complaint to tga: pain gone and pain gone plus€¦ · (26/03/2018) sent to the tga, for which i...

Complaint to TGA: Pain®Gone and Pain®Gone Plus

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Acknowledgment

The data on which this complaint is based was compiled by Jirayut Prompen, a Monash medical student, as part of a research project on evidence-based medicine.

Background

The CRP has previously upheld a complaint (2015/10/004) about a device with the same name “PainGone” (ARTG: 203804) that appeared to have an identical mode of operation (appended). The promotion of this device was determined to breach the Act section 41ML and Code sections 4(1)(b), 4(2)(a), 4(2)(b), 4(2)(c), 4(2)(f), 4(2)(g), 4(2)(h), 4(2)(i), 4(5), 5(2), 6(3)(c), 6(3)(d).

These devices also appear similar to “Pain Erazor” (ATG no: 276939) which won a 2017 Choice “Shonky” award, was the subject of a N.Z. Consumer review, and also a TGACRP complaint (26/03/2018) sent to the TGA, for which I can find no outcome.

This complaint

Regardless, Paingone and Paingone Plus are still being promoted for “relief from all types of pain including back & neck pain, arthritis, skeletal pain & aching muscles” and for “acute or chronic pain including muscle tension, nerve pain, neck soreness, foot discomfort, lower back pain, muscle cramps, knee pain and shoulder tension”. The web sites involved also have numerous dubious testimonials which require validation by statutory declarations.

Also, the names, “Pain Gone Pen” and “Pain Relief Erazor” are used as synonyms by the sponsor “Au Remedial.”

Pain®Gone and Pain®Gone Plus are $69.95 (no battery) and $84.95 (with battery) devices respectively.

I submit that this is a "high priority" complaint because the sponsor (&/or other advertisers) are recalcitrant, this type of product has had previous upheld complaints and the sponsor (and others) continue to make claims (documented below) that I allege breach the Therapeutic Goods Advertising Code 2015. This clearly impacts on the consumers ability to appropriately use these goods.

Publications:

• https://www.paingonepen.com.au

• https://paingonepen.com.au/product/paingone-plus/

• https://supportforaustralians.com.au/product/pain-gone-pen-pain-relief

• https://supportforaustralians.com.au/product/pain-gone-pen-plus-pain-relief-erazor-paingone

• https://todaytonightadelaide.com.au/stories/pain-away

• http://www.supportforaustralians.com.au/product/pain-gone-pen-pain-relief

• https://fishpond.com.au/Health/paingone-Plus-hand-held-pain-relief-device-for-conditions-such-as-arthritis-sciatica-joint-pain-cervical-spondylosis-back-shoulder-pain/5060035703272

• https://catch.com.au/product/pain-gone-pen-plus-pain-relief-erazor-paingone-2022371/?st=8&sid=112

• https://www.gumtree.com.au/s-pain+gone/k0?sort=rank

• https://www.youtube.com/watch?v=dDvp1qqKkLw

• Etc.

Date/Edition: 15/072018

Product: Pain®Gone and Pain®Gone Plus (ARTG no. 226635)

Sponsor: Au Remedial Pty Ltd, 35/2 Railway Parade, Lidcombe, NSW 2141 (ABN 67 622 271 658)

http://tgacrp.com.au/complaint-register/?_search=Pain&_id=2961

https://painerazor.com.au/

https://www.choice.com.au/shonky-awards/hall-of-shame/shonkys-2017/pain-erazor

https://www.choice.com.au/shonky-awards/hall-of-shame/shonkys-2017/pain-erazor

https://www.consumer.org.nz/articles/pain-erazor-claims

http://www.tgacrp.com.au/withdrawn-complaints/?_search=Erazor&_id=3310

https://painerazor.com.au/

https://painerazor.com.au/#reviews

https://painerazor.com.au/#reviews

https://supportforaustralians.com.au/product/pain-gone-pen-plus-pain-relief-erazor-paingone

https://www.paingonepen.com.au/

https://paingonepen.com.au/product/paingone-plus/

https://supportforaustralians.com.au/product/pain-gone-pen-pain-relief



https://todaytonightadelaide.com.au/stories/pain-away

http://www.supportforaustralians.com.au/product/pain-gone-pen-pain-relief

https://fishpond.com.au/Health/paingone-Plus-hand-held-pain-relief-device-for-conditions-such-as-arthritis-sciatica-joint-pain-cervical-spondylosis-back-shoulder-pain/5060035703272


https://catch.com.au/product/pain-gone-pen-plus-pain-relief-erazor-paingone-2022371/?st=8&sid=112

https://catch.com.au/product/pain-gone-pen-plus-pain-relief-erazor-paingone-2022371/?st=8&sid=112

https://www.gumtree.com.au/s-pain+gone/k0?sort=rank

https://www.youtube.com/watch?v=dDvp1qqKkLw


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Details of the complaint

The intended purpose of one of these devices (ARTG no. 226635) states:

“A device intended to be used to treat pain associated with musculoskeletal problems. An analgesic peripheral nerve stimulator consisting of an external stimulator and electrode placed on the skin not penetrating the body at any time, so the electrical stimulus is applied through the skin (transcutaneously) to the painful area. It typically includes several predetermined stimulation modulation options, e.g. pulse frequency or pulse duration. Portable, battery powered and worn on a belt or carried in a pocket.”

I allege that one or more of the following claims breach the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(b), 4(2)(c), 4(2)(d), 4(2)(f), 4(2)(g), 4(2)(h), 4(2)(i) and 5(2).

https://www.paingonepen.com.au

• The product name: o Pain gone.

• This handy device delivers a low-frequency electrical charge that helps to reduce the feeling of pain.

• No gels, accessories or batteries (see ARTG entry above)

• Even Works Through Light Clothing (not noted in trial below)

• Rigorous double-blind, placebo-controlled trial (unpublished, appended, see analysis below): o 83% of individuals with chronic pain who used the [Paingone] pen felt that their pain

had gone from severe to moderate or none”. o 65% of study participants reported extreme pain before using Paingone compared

to 10% after. o The study concluded that Paingone is effective in relieving general, acute and

chronic musculoskeletal pain


The product name:

• Pain gone

Product description

• Pain Gone transmits small electrical impulses that activate the nerve pathway. As a result the brain sends ‘signals’ to release endorphins (the body’s own natural relief mechanism).

• It allows the user to help relieve types of chronic and acute pain without using leads, pads or gels – just a simple 30 second treatment straight to the point of pain.

• Battery powered: No

Reviews

• Numerous positive testimonials which need verification by statutory declarations

Video https://youtu.be/sVrqGvT47oY

• "Safe and effective therapy"

• "As Paingone works by stimulating the body's natural pain killers it can be used for any type of pain and used anywhere on the body (except the head & eyes)."

• "As long as there is a minimum of 30-40 clicks it will be effective".


The product name:

• Pain gone

https://www.paingonepen.com.au/


https://youtu.be/sVrqGvT47oY



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Box

• "Fast simple drug-free pain relief"

Product description

• Paingone plus+ takes the trusted, TENS-like therapy of the original paingone and makes it even easier to use;

• For paingone plus, you only have to press the button once and the impulses are delivered automatically as it is battery powered.

• The standard paingone is manual and you have to click the button 30-40 times to receive the therapy.

Review

• One positive testimonial which need verification by statutory declarations


The product name:

• Pain gone

The claims:

• hand held pain relief device for conditions such as arthritis, sciatica, joint pain, cervical spondylosis, back & shoulder pain

• paingone plus takes the trusted, clinically-proven TENS-like therapy of the original paingone and makes it even easier to use;

The advertisements:

https://paingonepen.com.au (https://youtu.be/dDvp1qqKkLw)

Transcript: “Do you suffer daily from unwanted pain? Pain®Gone is a simple device used to reduce aches and pains. Pain®Gone works by creating pulses against the skin where you feel discomfort in the body. Make a difference to your day with Pain®Gone. Visit our website or call us today



https://paingonepen.com.au/

https://youtu.be/dDvp1qqKkLw


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https://paingonepen.com.au

The research (relevant articles appended):

To validate the claims made by Au Remedial Pty Ltd (the sponsor), the Cochrane review library, Ovid MEDLINE, and Monash University databases are searched to find the evidence to support the claims.

In addition, as the advertising website stated there was an unpublished “rigorous double-blind, placebo-controlled trial” on the effectiveness of Pain®Gone pen, a copy of this study was requested and kindly provided by the sponsor.



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The study provided by the sponsor

The clinical trial by Abellan (2017) titled, Randomized double-blind clinical trial to evaluate the efficacy of a handheld TENS pen in the treatment of acute or chronic musculoskeletal pain (appended) was used by the sponsor to support the claims.

This is an unpublished study of the effects of a TENS pen on acute and chronic musculoskeletal pain of varied etiology with the cohort of 86 participants. A 10-point visual analogue scales (VAS) was used to measure pain.1 The authors claimed that the TENS pen studied was effective in relieving acute and chronic musculoskeletal pain. However, there are several concerns about this study.

1. The research was carried out by Quantum Experimental S.L., a Spanish contract research company, on behalf of the device sponsor WinDirect S.L. Industry sponsored research has been shown to produce more favorable results than independent research.2

2. The experimental device used was described as a “portable piezoelectric stimulator”. It is unclear if is the same device as Pain®Gone (with no battery) or Pain®Gone Plus (with battery).

3. In section 4.3.1, it states, “the patients were assigned to one or another study group (placebo or experimental) by stratified randomization”. It is not clear what randomization method was used.

4. In section 4.3.2, it states the (active device) “produces an electrical output through the depression of the actuator button by the user. This results in the generation of a low energy electrical output.” The Paingone web site notes,

“Sensitivity to application of Paingone varies among users and by areas of the body. Some people find that they barely feel the pulses emitted. This is completely normal and does not indicate that there is a problem with the device. Other users find that each pulse delivers a small sensation to the skin”.3

The (placebo device) “emits no electrical impulse whatsoever…. upon depression of the activating button the metallic tip of the device protrudes by approximately 1-2mm from the unit casing”.

Thus, the active and placebo devices were not comparable and trial participants are likely to have known which one they received. In addition, there was no attempt to confirm blinding was effective; participants were not asked to speculate whether they were assigned to the active device or the placebo.

5. The number of patients investigated was relatively small: acute pain (29 active, 19 placebo) and chronic (20 active, 18 placebo). The numbers with varied types of pathology producing pain (or location of pain) were even smaller and not comparable between the active and placebo groups (Tables 5-7).

6. My calculation of the 95% confidence intervals of the mean difference in the VAS score before and after use in the total study population, and in the acute and chronic pain groups, (using results from Table 11) did not agree with the authors (Fig 2-4).

7. The paper (and advertisement) concluded that “83% of individuals with chronic pain who used the [Paingone] pen felt that their pain had gone from severe to moderate or none. The advertisement also stated that 65% of study participants reported extreme pain before using Paingone compared to 10% after. I could find no justification of these figures in the text or tables in the paper.

1 https://ncbi.nlm.nih.gov/pubmed/29321111 2 http://cochranelibrary-wiley.com/doi/10.1002/14651858.MR000033.pub3/full 3 https://paingonepen.com.au (FAQ What does Paingone feel like?)

https://ncbi.nlm.nih.gov/pubmed/29321111

http://cochranelibrary-wiley.com/doi/10.1002/14651858.MR000033.pub3/full



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Pain Treat N=

Mean VAS

before sample

SD SE of

mean

± 95% CI of

mean 95% CI of

mean from

Mean VAS

After sample

SD SE of

mean

± 95% CI of

mean 95% CI of

mean from

Acute E 29 4.9 2.1 0.39 0.76 5.66 4.14 3.8 2.4 0.45 0.87 4.67 2.93

P 19 6.2 1.9 0.44 0.85 7.05 5.35 5.5 1.8 0.41 0.81 6.31 4.69

Chronic E 20 6.6 1.8 0.40 0.79 7.39 5.81 5.7 2.1 0.47 0.92 6.62 4.78

P 18 4.9 2.0 0.47 0.92 5.82 3.98 4.7 2.0 0.47 0.92 5.62 3.78

Total E 49 5.7 2.1 0.30 0.59 6.29 5.11 4.7 2.5 0.36 0.70 5.40 4.00

P 37 5.4 2.1 0.35 0.68 6.08 4.72 5.1 2.0 0.33 0.64 5.74 4.46

Total 86

Above from Table 11, results graphed below. As 95% CI of means overlap the difference is not statistically significant

2.5

3

3.5

4

4.5

5

5.5

6

VA

S

Acute pain VAS in experimental group (95% CI)

Befor After

4

4.5

5

5.5

6

6.5

7

7.5

8

VA

S

Chronic pain VAS in experimental group (95% CI)

Befor After


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Other relevant studies (attached)

The published research done by Blenkinship et al (2011) investigated hypoalgesic effects of wide range of TENS-like device including Pain®Gone pen. The results show that there is no significant difference in placebo group and the experimental group in altering thermal thresholds for sensation or pain.

A conference communication by Ivanova-Stoilova and Howells (2000) described that 22 out of 36 patients with chronic musculoskeletal pain reported pain relief after using Pain®Gone pen. However, this study had a very small sample size and no placebo-controlled group. It is likely that the pain-relieving effects were produced by the placebo effect of administering the device rather than any active mechanism within the device.

The published research by Johnson (2001) concluded that “claims by manufacturers about the specificity and extent of effects produced using TENS-like devices are overstated” because there is no good quality research supported.

Conclusion

The studies supporting Pain®Gone pens are low quality, unpublished and have a small sample size. They do not support the strong claims made for these devices. The claims made by the sponsor refer to the effectiveness of electrical nerve stimulation (TENS) devices but Pain®Gone pen is TENS-like device with a different mechanism of action and its effectiveness has not yet to be supported by a good quality research. In short, the numerous claims made for this device are misleading, deceptive and breach the Therapeutic Goods Advertising Code 2015.

Bibliography:

Abellan, J. (2017), Randomised double-blind clinical trial to evaluate the efficacy of a handheld TENS pen in the treatment of acute or chronic musculoskeletal pain, quantum experimental, Murcia, Spain

Blenkinship, A., Benham, A., Tashani, O. and Johnson, M. (2011). An Investigation into the Hypoalgesic Effects of Transcutaneous Piezoelectric Current on Experimentally Induced Thermal Stimuli in Healthy Participants. Neuromodulation: Technology at the Neural Interface, 14(3), pp.242-248.

Ivanova-Stoilova T., Howells D. (2002), The usefulness of PainGone pain killing pen for self-treatment of chronic musculoskeletal pain-a pilot study. The pain Society Scientific meeting 2002; abstract 104.

Johnson, M. (2001). Transcutaneous Electrical Nerve Stimulation (TENS) and TENS-like devices: do they provide pain relief?. Pain Reviews, 8(3-4), pp.121-158.

Dr Ken Harvey MBBS, FRCPA, AM Associate Professor Department of Epidemiology and Preventive Medicine

School of Public Health and Preventive Medicine

Monash University Alfred Campus 553 St Kilda Rd Melbourne VIC 3004 Mobile: +61 419181910 Email: [email protected] WWW: www.medreach.com.au 15 July 2018

mailto:[email protected]

http://www.medreach.com.au/

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COMPLAINTS RESOLUTION PANEL DETERMINATION

Complaint 2015-10-004 PainGone

ARTG ID: 203804

Meeting held 3 December 2015

Complaint summary^

Complainant Anonymous

Advertiser uHealth Australia Pty Ltd

Subject matter of

complaint Internet advertisement

Type of determination Final

Sections of the Code,

Regulations or Act found

to have been breached*

Act section 41ML

Code sections 4(1)(b), 4(2)(a), 4(2)(b), 4(2)(c), 4(2)(f), 4(2)(g), 4(2)(h),

4(2)(i), 4(5), 5(2), 6(3)(c), 6(3)(d)

Sections of the Code,

Regulations or Act found

not to have been breached*

None

Sanctions

Withdrawal of advertisement

Withdrawal of representations

* only sections of the Code, Act, or Regulations that were part of the complaint or were raised by

the Panel are listed

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The advertisement(s)^

1. The complaint concerned an internet advertisement published at www.uhealth-aus.com,

viewed by the complainant on 16 October 2015.

2. The advertisement was a website product page comprising a picture of the device, a heading

“Fast and Effective Drug Free Therapy”, some text including the wording “The PainGone

pen works on the principles of Transcutaneous Electrical Nerve Stimulation (also known as

TENS or TNS). PainGone is now widely accepted as a breakthrough in TNS therapy, which

is a clinically tested and well known treatment used by millions worldwide.”, a link to

tutorials on how to use the product and more text, which included the following

representations: “The PainGone treatment is an easy to use device to address pain”; “..instant

relief wherever it’s needed.”; “fast and effective relief from pain quickly and discreetly”;

“The PainGone pen is clinically proven and has applications across many diseases and causes

of pain.”; “if you suffer from chronic conditions such as arthritis, rheumatism, sciatic,

osteoporosis, the Paingone pen is a clinically tested alternative to many traditional relief

therapies. There are many benefits of using the PainGone Pen over other forms of relief.”;

“100% Natural Drug-Free Therapy”; “Many sufferers are worried about the risks associated

with pain killers including side effect, dependency and overdose”; and other representations.

3. An excerpt of the advertisement can be viewed in the relevant Appendix to this

determination.

The product(s)

4. The advertisement promoted the product PainGone (ARTG ID: 203804).

The advertiser(s)

5. The advertiser was uHealth Australia Pty Ltd.

The complaint^

6. The complainant was anonymous.

7. The complainant alleged that the advertisement breached the Code in the following respects:

a) Sections 4(2)(g), 4(2)(h) and 4(2)(c) of the Code because “The name PainGone implies

that the product is guaranteed to treat your pain issues and that the pain will be ‘gone’

(rather than improved, assisted, may help etc.), and therefore implying that the product is

effective in all cases. This is misleading.”

b) Sections 4(1)(b), 4(2)(a) and 4(2)(c) of the Code because “The information under “What

is Paingone?” includes breaches such as…“instant relief” and “The PainGone pen is

clinically proven and has applications across many diseases and causes of pain. If you

suffer from chronic conditions such as arthritis, rheumatism, sciatica, osteoporosis, the

Paingone pen is a clinically tested alternative to many traditional relief therapies.”

c) Section 4(2)(i) of the Code with respect to “totally safe” and “PainGone is extremely safe

to use”

d) Section 4(2)(f) of the Code with respect to “Use As Frequently As You Wish” and

“Being a drug-free and totally safe alternative relief treatment means you can use

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PainGone as often as you like. Whenever you feel a twinge, ache or throb, PainGone is

just a click away.”

e) Section 4(5) of the Code with respect to “Many sufferers are worried about the risks

associated with pain killers including side effects, dependency and overdose. For these

pain sufferers the opportunity to ease their pain naturally with an alternative pain relief

treatment is a very welcome.”

f) Section 5(2) of the Code “because of claims about chronic conditions, arthritis,

rheumatism, sciatica and osteoporosis”

g) Sections 4(2)(c), 4(2)(f) and 4(2)(i) of the Code because “The information under

“Frequently Asked Questions” includes breaches such as…“How often should I use

PainGone? You can use PainGone as often as you require. It’s 100% natural, drug-free

therapy so you cannot overdose and there are no side effects.”

h) Sections 6(3)(c) and 6(3)(d) of the Code because “no page on the website has the

mandatory statements”

Additional matters raised by the Panel

8. Under sub-regulation 42ZCAH(1), the Panel is empowered to raise matters other than those

specified in the complaint, where the Panel is satisfied that the advertisement to which the

complaint relates contains matters that are not mentioned in the complaint, which may

contravene the Act, Regulations, or the Code in other ways. The Panel was so satisfied and

raised as additional matters, possible breaches of:

Section 41ML of the Act because the advertisement may be advertising the product for a

purpose other than the intended purpose accepted in relation to the inclusion on the

Register, including the name of the product

Sections 4(1)(b), 4(2)(a) and 4(2)(c) of the Code because of the claim “100% Natural”

Section 4(2)(b) of the Code because the advertisement may lead consumers to

inappropriately treating potentially serious conditions or diseases, such as those identified

by the complainant in relation to the alleged breach of section 5(2) of the Code

The advertiser’s response to the complaint^

9. In response to the complaint, the advertiser stated “In response to the information provided

we have removed the “Paingone” product from our website and ceased all promotional

activities pending a review of the claims and advertising material in consultation with the

manufacturer.”

10. No other response was made to address the specific matters raised by the complainant and

the Panel.

Findings of the Panel

11. Section 41ML of the Act states that a person commits an offence if the person by any means

advertises a medical device as being for a purpose, the device is included in the Register and

the purpose is not a purpose accepted in relation to that inclusion.

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12. The intended purpose for this product is “to provide analgesic electrical stimulus to reduce

the perception of pain by electrically stimulating peripheral nerves across the skin

(transcutaneously).”

13. The Panel was of the view that the claims for pain relief in the advertisement went far

beyond “perception” of pain, referring to the device as a ‘treatment’ in the context of serious

conditions, ailments and defects. The Panel was, therefore, satisfied that the advertisement

breached section 41ML of the Act.

14. The Panel found, therefore, that this aspect of the complaint was justified.

15. Section 4(1)(b) of the Code requires that advertisements for therapeutic goods “contain

correct and balanced statements only and claims which the sponsor has already verified.”

Section 4(2)(a) of the Code prohibits representations that are “likely to arouse unwarranted

and unrealistic expectations of product effectiveness”. Section 4(2)(c) of the Code prohibits

representations that “mislead directly or by implication or through emphasis, comparisons,

contrasts or omissions”.

16. The Panel notes that the Panel’s letter seeking a response from an advertiser makes it very

clear that all relevant material should be provided to the Panel in the first instance, by stating

“You should respond fully to the complaint. If you do not provide a response, or

provide only a partial or provisional response, the Panel may determine the complaint

on the basis of the material before it.” No substantiating material whatsoever was provided

with the response.

17. In the absence of any substantiating material and substantive response to the specific matters

raised, the Panel was satisfied that the advertisement was unverified, was likely to arouse

unwarranted and unrealistic expectations of product effectiveness and was misleading, in

breach of sections 4(1)(b), 4(2)(a) and 4(2)(c) of the Code, through claims including “instant

relief”, “The PainGone pen is clinically proven and has applications across many diseases

and causes of pain. If you suffer from chronic conditions such as arthritis, rheumatism,

sciatica, osteoporosis, the Paingone pen is a clinically tested alternative to many traditional

relief therapies” and “100% Natural”.

18. The Panel found, therefore, that these aspects of the complaint were justified.

19. Section 4(2)(f) of the Code prohibits representations that “encourage inappropriate or

excessive use” of therapeutic goods.

20. The Panel was satisfied that the claims “Use As Frequently As You Wish” and “Being a

drug-free and totally safe alternative relief treatment means you can use PainGone as often as

you like. Whenever you feel a twinge, ache or throb, PainGone is just a click away.”,

particularly in the context of claims of treatment of serious diseases, were likely to encourage

inappropriate use of therapeutic goods.


22. Section 4(2)(g) of the Code prohibits representations that therapeutic goods are “infallible,

unfailing, magical, miraculous”, or that they are “a certain, guaranteed or sure cure”. Section

4(2)(h) of the Code prohibits advertisements for therapeutic goods that “contain any claim,

statement or implication that it is effective in all cases of a condition”.

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23. The Panel agreed with the complainant that “the name PainGone implies that the product is

guaranteed to treat your pain issues and that the pain will be ‘gone’ (rather than improved,

assisted, may help etc.), and therefore implying that the product is effective in all cases. This

is misleading.” and was satisfied that the advertisement breached sections 4(2)(g), 4(2)(h)

and 4(2)(c) of the Code as alleged, finding that the product name itself, as used in the

advertisement, conveyed that the product would be infallible, guaranteed or permanently and

invariably effective in all cases of a condition.


25. Section 4(2)(i) of the Code prohibits representations that the goods advertised are completely

safe, harmless, or free of side-effects.

26. The Panel was satisfied that the advertisement was in breach of this section of the Code

through the inclusion of wording such as “totally safe”, “PainGone is extremely safe to use”

and “It’s 100% natural, drug-free therapy so you cannot overdose and there are no side

effects”.


28. Section 4(5) of the Code requires that comparisons made in advertisements must be balanced

and must not be misleading or likely to be misleading, and prohibits the inclusion in

advertisements of comparisons that “imply that the therapeutic goods, or classes of

therapeutic goods, with which comparison is made, are harmful or ineffectual.”

29. The Panel was satisfied that the advertisement was in breach this section of the Code because

the claim “Many sufferers are worried about the risks associated with pain killers including

side effects, dependency and overdose. For these pain sufferers the opportunity to ease their

pain naturally with an alternative pain relief treatment is a very welcome.” was a comparative

claim that, in the absence of any substantiating data, was not supported and was therefore

misleading, and also implied that the therapeutic goods with which the comparison was

made, are harmful.


31. Section 5(2) of the Code prohibits advertisements that “refer, expressly or by implication, to

serious forms of diseases, conditions, ailments or defects specified in Part 2 of Appendix 6,

unless prior approval is given under the Therapeutic Goods Act 1989.” The diseases and

conditions specified in Part 2 of Appendix 6 of the Code include “serious forms of” a wide

range of health concerns.

32. In relation to the alleged breach of section 5(2) of the Code, which included a reference to

arthritis, the Panel noted that the word “arthritis” can refer to a number of conditions

including osteoarthritis and rheumatoid arthritis and, less commonly, other conditions such as

gout. The word “arthritis”, when used without clear qualification in an advertisement

directed to consumers, may refer to joint disease of any severity or type. Because such a

reference is not specific as to the type of arthritis, it is likely to be taken to refer to cases of

arthritis that have not yet been diagnosed by a qualified healthcare professional. The Panel is

of the view that, where arthritis is referred to without qualification in an advertisement, the

reference can refer to forms of joint disease that are:

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generally accepted not to be appropriate to be diagnosed and/or treated without

consulting a suitable healthcare professional; and,

generally accepted to be beyond the ability of the average consumer to evaluate

accurately and to treat safely without regular supervision by a qualified healthcare

professional.

33. Furthermore, where an unqualified reference to arthritis is made, it is likely that a consumer

will interpret the reference as extending to serious forms of arthritis, including rheumatoid

arthritis. This interpretation is less likely to occur if a reference is confined to osteoarthritis

and is qualified by words such as “mild” or “minor”. Where a reference is confined to

osteoarthritis, the context in which a claim is made, including images and language used, and

whether or not a claim is qualified by “temporary” or “symptomatic” relief, will be relevant.

34. The Panel was satisfied that the unqualified reference to arthritis in the advertisement was in

breach of section 5(2) of the Code. Additionally, the Panel was satisfied that the unqualified

reference to sciatica and the reference to osteoporosis were also references to serious

conditions, in breach of section 5(2) of the Code.

35. The Panel found, therefore, that this aspect the complaint was justified.

36. Section 4(2)(b) of the Code prohibits advertisements that are “likely to lead to consumers

self-diagnosing or inappropriately treating potentially serious diseases”.

37. The Panel was satisfied that the references in the advertisement to sciatica and osteoporosis,

as well as to arthritis where not sufficiently qualified, were references likely to lead

consumers to self-diagnosing or inappropriately treating these potentially serious diseases, in

breach of section 4(2)(b) of the Code.

38. The Panel found, therefore, that this aspect the complaint was justified.

39. The advertisement ought to have included the words “always read the label” (section 6(3)(c)

of the Code), as well as the words “use only as directed” and “if symptoms persist see your

doctor/healthcare professional” (section 6(3)(d) of the Code). The advertisement did not

include these mandatory statements.


Sanctions

41. The Panel requests uHealth Australia Pty Ltd, in accordance with subregulation 42ZCAI(1)

of the Therapeutic Goods Regulations 1990:

a) to withdraw the advertisement from further publication;

b) to withdraw all the representations noted above as having breached the Code, including

any reference to serious diseases, conditions, ailments or defects;

c) not to use the representations in (b) above in any other advertisement*;

d) where the representation has been provided to other parties such as retailers or website

publishers, and where there is a reasonable likelihood that the representation has been

of 9

published or is intended to be published by such parties, to advise those parties that the

representation(s) should be withdrawn;

e) within 14 days of being notified of this request, to provide evidence to the Panel of its

compliance, including a response in writing that it will comply with the Panel’s

sanctions, and where appropriate, supporting material such as copies of instructions to

advertising agents or publishers, or correspondence with retailers and other third party

advertisers.

42. The advertiser’s attention is drawn to the provisions of sub-regulations 42ZCAI(3) and (4)

which permit the Panel to make recommendations to the Secretary in the event of non-

compliance with this request.

Dated 27 June 2016

For the Panel

Judith Brimer

Executive Officer

of 9

Appendix A: Definitions and footnotes

In this determination, unless otherwise specified:

a) “the Act” means the Therapeutic Goods Act 1989;

b) “the Regulations” means the Therapeutic Goods Regulations 1990;

c) “the Code” means the Therapeutic Goods Advertising Code;

d) “the Register” means the Australian Register of Therapeutic Goods;

e) “any other advertisement” appearing in sub-regulation 42ZCA1(1)(d) is not confined to

advertisements in specified or broadcast media (in relation to which complaints may be

made to the Panel under Regulation 42ZCAB). It should be noted that HTML metatags

and other information which can be retrieved by internet search engines, whether or not it

is ordinarily viewed directly by consumers, constitutes advertisement material.

^Readers of the determination should note that the sections “complaint summary”, “the advertisement(s)”, “the

complaint”, and “[a party]’s response to the complaint”, are summaries that are intended to aid readers of this

document. In reaching its decision, the Panel considered all of the material before it, including material that may

not be mentioned specifically in the summaries. The summaries do not form part of the Panel’s reasoning.

*Under regulation 42ZCAI of the Regulations, the Panel may request that a representation not be used in any other

advertisement unless the advertiser satisfies the Panel that the use of the representation would not result in a

contravention of the Therapeutic Goods Act 1989, the Therapeutic Goods Regulations 1990 or the Therapeutic

Goods Advertising Code. Under the Panel’s procedures, the Panel will not ordinarily give additional consideration

to such a matter unless significant new material that was not available at the time of the Panel’s determination has

become available, or until at least 12 months have passed since the Panel’s request was made.

of 9

Appendix B: Excerpt of the Advertisement

Public Summary Summary for ARTG Entry: 226635 AU Remedials - Stimulator, electrical, analgesic, peripheral nerve, transcutaneous

ARTG entry for Medical Device Included Class IIa

Sponsor AU Remedials

Postal Address 8 / 11-15 Refactory Court,HOLROYD, NSW, 2142 Australia

ARTG Start Date 7/08/2014

Product category Medical Device Class IIa

Status Active

Approval area Medical Devices

Conditions

- The inclusion of the kind of device in the ARTG is subject to compliance with all conditions placed or imposed on the ARTG entry. Refer Part 4-5, Division 2 (Conditions) of the Therapeutic Goods Act 1989 and Part 5, Division 5.2 (Conditions) of the Therapeutic Goods (Medical Devices) Regulations2002 for relevant information.- Breaching conditions of the inclusion related to the device of the kind may lead to suspension or cancellation of the ARTG entry; may be a criminal offence; and civil penalties may apply.

ManufacturersName AddressCounter Scientific Development GZ Ltd 2-3F Building 6 Dapian Industrial Zone Tangxia

RoadTianhe District Guangzhou, Guangdong, 510665 China

Products

1. Stimulator, electrical, analgesic, peripheral nerve, transcutaneous

Product Type Single Device Product Effective date 7/08/2014

GMDN 35372 Analgesic TENS system

Intended purpose A device intended to be used to treat pain associated with musculoskeletal problems.An analgesic peripheral nerve stimulator consisting of an external stimulator and electrode placed on the skin not penetrating the body at any time, so the electrical stimulus is applied through the skin (transcutaneously) to the painful area.It typically includes several predetermined stimulation modulation options, e.g. pulse frequency or pulse duration.Portable, battery powered and worn on a belt or carried in a pocket.

Specific Conditions

No Specific Conditions included on Record

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summ

ary

Page 1 of 1 Produced at 15.07.2018 at 08:52:05 AESTThis is not an ARTG Certificate document.The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown. Visit www.tga.gov.au for contact information

http://www.tga.gov.au/about/website-copyright.htm

Final Report 4-01-2017 Cód. QTM/WND-0215

Page:1/45

FINAL REPORT

Date 4-01-2017

N. of pages 46

Protocol code QTM/WND-

0215

RANDOMIZED DOUBLE-BLIND CLINICAL TRIAL TO EVALUATE THE

EFFICACY OF A HANDHELD TENS PEN IN THE TREATMENT OF ACUTE

OR CHRONIC MUSCULOSKELETAL PAIN

Protocol code: QTM/WND-0215

Sponsor: WINDIRECT, S.L.

INDEX

1. GENERAL INFORMATION 2


Page:2/45

2. BACKGROUND AND STUDY JUSTIFICATION 4

3. OBJECTIVES OF THE TRIAL 6

4. TRIAL DESIGN 8

4.1. Trial design 8

4.2. Trial Variables 9

4.2.1. Primary endpoint 10

4.2.2. Secondary variables 10

4.3. Measures to minimize or avoid bias 11

4.3.1. Randomization 11

4.3.2. Masking techniques and blinding 11

4.4. Description of investigational products 11

4.5. Acquisition, packaging and labelling of medication 12

4.6. Storage and dispensation 13

4.7. Identification of data to be recorded in the CRF 13

4.8. End of the study 13

5. SELECTION AND WITHDRAWAL OF PATIENTS 13

5.1. Definition of the study population 13

Inclusion Criteria 13

Exclusion Criteria 14

6. STATISTICS 15

6.1. Statistical methodology 15

7. RESULTS 15

7.1. Demographic variables 16

7.1.1. Age 16

7.1.2. Sex 16

7.2. Clinical variables 17

7.3. Efficacy analysis. Visual analogue scale (VAS) 19

7.3.3. Temporary evolution of the daily VAS scores 24

7.4. Daily use of the device 36

7.5. Use of rescue medication. 38

7.6. Quality of life questionnaire. 39

8. TOLERANCE AND SAFETY 44

9. CONCLUSIONS 45

1. GENERAL INFORMATION


Page:3/45

Title: Randomized double-blind clinical trial to evaluate the efficacy of a handheld

TENS pen in the treatment of acute or chronic musculoskeletal pain.

Protocol code: QTM/WND-0215

Sponsor data

WINDIRECT, S.L. C/ Córcega, 299, 5º 3ª I

08008 Barcelona

Spain

Principal Investigator

Juan Francisco Abellán

Investigation Site

Hospital General Universitario Morales Meseguer

Study duration

● Total duration of study: 8 months

● Recruitment: 6 months

● Treatment: 28 days

● Results and final report: 1 month

Independent Ethics Committee (IEC)

IRB Hospital General Universitario Morales Meseguer

Contract Research Organization (CRO)

Quantum Experimental, S.L.

C/ Carril de la Condesa Nº 58, office 505

30010 Murcia, Spain


Page:4/45

2. BACKGROUND AND STUDY JUSTIFICATION

The International Association for the Study of Pain (IASP), (2) defines pain as an

unpleasant sensory and emotional experience associated with actual or potential tissue

damage, or described in terms of such damage. There are two kinds of pain, acute and

chronic. The acute pain is a predominant symptom or manifestation of tissue injury,

chronic pain is considered a disease in itself. Chronic pain persists for a period longer

than three months and often it is difficult to treat. It can cause major problems to the

patient and it has a negative impact on their quality of life.

Chronic pain is classified in oncological and non-oncological. Both can be nociceptive

(somatic or visceral) and neuropathic.

In scientific literature there is a broad consensus that pain is a complex and

multifactorial phenomenon that depends on the interaction of physiological,

psychological and sociocultural factors. Inconclusive differences in pain perception or

manifestation, related to ethnic or racial conditions in adults and children have been

described (12, 13, 14).

There are studies that show differences in pain perception by gender, highlighting the

revision published in 2009 about prevalence of chronic pain in representative samples

from different countries of our socioeconomic environment. In seven out of ten studies

included, the differences between men and women were statistically significant.

Different types of pain based on its causation, characteristics and approach have been

conceptualized. In 1994 IASP published a classification of chronic pain, which included

a complete taxonomy and different definitions; both are subject to periodic revision and

updates, (16).

The following table shows the common causes of chronic pain, (4):


Page:5/45

Table1. Common causes of chronic pain

Musculoskeletal pain Joint pain (arthritis and arthrosis) Spinal pain: lumbar, cervical Muscle pain (myofascial pain syndromes and muscular pain)

Oncological pain with musculoskeletal affectation

Neuropathic pain Herpes zoster and post-herpetic neuralgia Neuralgia of peripheral nerves

Painful diabetic neuropathy Complex regional pain syndromes Pain from nerve injury Post-amputation pain and phantom limb

Mixed pain Radicular pain of spinal pathology

Chronic visceral pain

Vascular pain

Somatoform pain

The pain from musculoskeletal injuries is one of the most common reasons for

disability. In addition, these injuries can create functional impairment, disrupt sleep and

mood, and this cannot be completely solved with currently available therapies which

enable the incorporation of additional treatment options to potentially improve

outcomes of care.

Recent research has examined the use of an adjuvant transcutaneous electrical nerve

stimulator (TENS) for pain treatment.

In 1965, Melzack and Wall introduced “gate-control theory” about an electrical current

that affects nerve fibers. This stimulation causes the release of endorphins in the

hypothalamus which gives relief from pain especially that of musculoskeletal origin.

Following this theory more clinical trials were carried out. All of them showed positive

results regarding the effect of pain relief. Based on this technology the studied device is

a handheld, wireless TENS electrical stimulator.

This trial is going to examine specifically if the addition of a protocol transcutaneous

electrical nerve stimulation (TENS) therapy (handheld TENS pen) will have a beneficial

impact on pain caused by acute and chronic musculoskeletal injury.

The types of pain covering acute or chronic musculoskeletal injury for this study are the

following:

- Neck and shoulders: neck tension syndrome, cervical syndrome, torticollis and

frozen shoulder.


Page:6/45

- Arms and elbow: epicondylitis (tennis elbow), epitrocleitis (golfer’s elbow),

tenosynovitis in extensor (elbow bursitis), radial tunnel (radial nerve by repeated

movements of the arm), wrist tendinitis (rotator cuff syndrome and sprained

wrist).

- In the hand and wrist: carpal tunnel syndrome; ulnar tunnel syndrome; Clerk

syndrome.

- In the spine: back pain, acute lower back pain, acute lumbar pain.

- In the lower limbs: Achilles tendinitis; knee bursitis

- Arthritis, osteoarthritis, rheumatism

Bibliography

2. Unidad de Cirugía Mayor Ambulatoria. Estándares y Recomendaciones. Agencia de

Calidad del SNS. Ministerio de Sanidad y Consumo. 2008.

4. Unidad de Pacientes Pluripatológicos. Estándares y Recomendaciones. Agencia de

Calidad del SNS. Ministerio de Sanidad y Política Social. 2009.

12. Green CR, Anderson KO, Baker TA, Campbell LC, Decker S, Fillingim RB, et al.

The unequal burden of pain: Confronting racial and ethnic disparities in pain. Pain Med

2003; 4: 277-294.

13. Anderson KO, Green CR, Payne. Racial and ethnic disparities in pain: causes and

consequences of unequal care. J Pain. 2009;10:1 187-204.

14. Flores G; Committee On Pediatric Research Technical report--racial and ethnic

disparities in the health and health care of children. Pediatrics. 2010.

15. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL. Sex,

Gender, and Pain: A Review of Recent Clinical and Experimental Findings. J Pain.

2009; 10: 447- 485.

16. International Association for the Study of Pain. Task Force on Taxonomy.

Classification of Chronic Pain, Second Edition, edited by H. Merskey and N. Bogduk,

IASP Press, Seattle, 1994.

3. OBJECTIVES OF THE TRIAL


Page:7/45

3.1. Main objectives

● To evaluate the efficacy of the handheld TENS pen for the relief of acute pain

of moderate/severe intensity associated with musculoskeletal disorders

compared with a placebo.

● To evaluate the efficacy of the handheld TENS pen for the relief of chronic

pain of moderate/severe intensity associated with musculoskeletal disorders

compared with a placebo.

3.2.Secondary objectives

● To compare the efficacy of the handheld TENS pen for the relief of acute pain

associated with musculoskeletal diseases versus chronic pain.

● To compare the modifications that the handheld TENS pen produces in the

administration of analgesic medication versus a placebo for both chronic and

acute pain associated with musculoskeletal disorders.

● To evaluate the modifications that the handheld TENS pen produces in the

quality of life of patients with musculoskeletal disorders compared to a placebo.

● To evaluate the safety and tolerability of the handheld TENS pen.

Definition

The International Association for the Study of Pain (IASP) defined pain as “an

unpleasant sensory and emotional experience associated with actual or potential tissue

damage, or described in terms of such damage”

Classification of pain according to duration

Acute pain: Initially acute pain was simply defined in terms of duration, but now it is

defined as “an unpleasant and complex experience with cognitive and sensory factors

that occur in response to tissue trauma”.

In contrast to chronic pain, with acute pain there is a significant correlation between the

intensity of pain and the trigger disease and it gradually reduces until it disappears, once

the healing of the underlying injury occurs.

Chronic pain: Defined as “pain that extends for over 3 or 6 months from the appearance

or extending beyond the period of healing of tissue damage, or is associated with a


Page:8/45

chronic medical condition”. Other features of chronic pain in addition to the time

factor, are that sometimes the possibilities to identify the causal pathology is low. It can

be insufficient to explain the presence and intensity of the pain, and there can be a poor

response to standard treatments.

Intensity of moderate/severe pain: Equivalent to a score higher than 4 on the visual

analog scale of pain intensity.

Type of medication

Control medication (scheduled): Medication prescribed by the doctor on a schedule in

order to keep the individual the least amount of time with pain.

Rescue medication: Medication prescribed by the doctor to be used by the patient on

demand at times when the intensity of the pain makes neccesary its use

4. TRIAL DESIGN

4.1.Trial design

This is a multicenter, randomized, placebo-controlled, parallel, double-blind clinical

trial.

In this trial, stratified randomization was done depending on the duration of the pain

associated with musculoskeletal disorders experienced by the patients. Therefore, strata

are acute pain and chronic pain.

In each stratum the patient allocation was performed to one treatment group in a 1:1

ratio. Furthermore the relationship between the number of patients in the experimental

group and the placebo group was also be 1:1.

Figure 1 shows the scheme of the trial design.

During the visit 0 or selection visit the patients were recruited. After informed consent

was signed they were randomized. This visit could be made during the 15 days prior to

the initiation of treatment.


Page:9/45

Figure1.Clinical Trial Design

Visit 1, which corresponds to day 0 of the study, it is the baseline and could coincide

with the screening visit. From this visit, treatment with investigational medical devices

was initiated.

Visit 2 and 3 correspond to day 14 and 28 of the study, respectively. In all visits, the

patients had to go to the research centre to carry out the study procedures.

Treatment groups:

Experimental group (A): Handheld TENS pen

Placebo group (B): placebo

The clinical trial is double blind so that neither the researchers nor the patients know

which group they have been assigned to. This is intended to reduce to a minimum the

subjectivity of patients and researchers and reduce the bias in the interpretation of

results.

This clinical trial was carried out in the Morales Meseguer Hospital (reference centre)

and 3 primary care centres in which the researchers developed their activity. In this

study they were employed by the Public Health Service of Murcia. In addition, these

researchers included patients from other private clinics where the prevalence of acute

pain was greater in respect to the reference hospital.

This design is justified by the need to cover as representative a sample as possible of the

study population.

4.2. Trial Variables


Page:10/45

4.2.1. Primary endpoint

The primary endpoint of efficacy is the intensity of the pain of musculoskeletal origin.

To measure the intensity of the pain, the visual analogue scale (VAS) was used. VAS is

a line of 10 cm graded numerically from 0 to 10 in which the patient marks pain

intensity of 0-10 considering that 0 is “nothing” and 10 is “intolerable”. The distance in

centimetres or millimetres, from the point of “no pain” marked by the patient is the pain

intensity. Studies show that the value of the scale reliably reflects the intensity of pain

and its evolution. Therefore it is used to assess the intensity of pain experienced by a

person over time.

A value less than 4 in the VAS means mild or mild to moderate pain, a value between 4

and 6 implies the presence of moderate to severe pain, and more than 6 implies the

presence of severe pain.

The assessment of pain relief by VAS was done by two methods:

Daily analysis of the variable: Pain was measured by VAS each morning before

administering any pain medication and before the application of the investigational

device.

Analysis during the use of the device throughout the study: When the subject

decided to use the device, they had to measure the intensity of pain using the VAS,

before the device application and two minutes after its use. These measurements were

performed each time the individual used the device throughout the day.

4.2.2. Secondary variables

● Demographic variables: age and sex.

● Clinical variables: disease process that causes pain, duration of pain, location,

basal intensity, type of pain (acute or chronic)

● Concomitant analgesic medication.

● Daily use of the device. Number of times the device is used daily. The evolution

of this variable will be analyzed throughout the observation period.

● Quality of life. The quality of life will be measured by the EQ-5D scale. They

apply at baseline and at the final visit.

● The safety and tolerability of the product will be assessed by analysis of adverse

events detected and recorded throughout the study.


Page:11/45

4.3. Measures to minimize or avoid bias

4.3.1. Randomization

Patients who were candidates to be included in the study were selected consecutively

assigning a selection number.

Once it had been verified that the patient met all inclusion criteria and none of the

exclusion criteria and they had signed the informed consent form, the patients were

assigned to one or another study group (placebo or experimental) by stratified

randomization.

4.3.2. Masking techniques and blinding

As explained above, this is a double blind study. So, the placebo had identical

characteristics and the same appearance as the medical device under investigation but

no activity. Both were manufactured by the sponsor.

4.4. Description of investigational products

Experimental product:

Portable piezoelectric stimulator based on transcutaneous electrical nerve stimulation

(TENS) with EC Nº 94387

The device is a handheld, wireless TENS electrical stimulator, ergonomically designed

with a pen-like shape to fit to the hand and allow for easy use. Externally, it consists of

an electrically-insulating casing, with at one end an actuator button, and at the other end

a contact electrode. In the middle of the device is a metal contact ring that earths the

device.

The device is intended for pain relief and works on the basis of transcutaneous electrical

nerve stimulation. It device generates low-energy electrical impulses which is posited to

result in pain relief through the same biological mechanism as that of other TENS

devices.

The device produces an electrical output through the depression of the actuator button

by the user. This results in the generation of a low energy electrical output, which is

conducted through the negative electrode to the user’s skin at the site of application of

the device. The device is a complete unit and does not require any additional


Page:12/45

accessories. It is designed for use directly by the end-user.

Therapeutic group: Medical Device Class IIa

Category:

4- Electro/mechanic products

12- Products that use radiation for diagnostics

GMDN (Global Medical Device Nomenclature):

35372- Stimulator, electrical, analgesic, peripheral nerve, transcutaneous

Patents: EP1194107 A1/WO2001001920 A1

How to use: The individual holds the device in their hand with their fingers placed

firmly around the metal ring. The thumb should be free to press the activation button.

The tip of the device is placed directly onto the painful area and the button is pressed 30

to 40 times.

Placebo Product:

The placebo device is identical in external form to the genuine medical device and is

comparable in weight. However, the placebo unit emits no electrical impulse

whatsoever.

Instead, upon depression of the activating button, the metallic tip of the device protrudes

by approximately 1-2mm from the unit casing. This brings the tip into contact with the

user’s skin, or presses more deeply into clothing. Upon release of the button, the tip

recedes back into the casing. The intention is to give an impression to the user that the

placebo device is active (while having no therapeutic benefit) and obstructing the user

from discerning the placebo from the genuine article.

The following paragraphs apply to both the experimental and the placebo product.

How to use: The individual holds the device in their hand with their fingers placed

firmly around the metal ring. The thumb should be free to press the activation button.

The tip of the device is placed directly onto the painful area and the button is pressed 30

to 40 times.

4.5. Acquisition, packaging and labelling of medication

The sponsor was responsible for the manufacturing, mask, coding and product supply of


Page:13/45

both the experimental and the placebo devices.

Investigational products (IPs) were properly labelled according to the Guide to Good

Manufacturing of medicines for human and veterinary use.

4.6. Storage and dispensation

The sponsor was responsible for sending the investigational product to the Hospital

where it was stored at the appropriate temperature and humidity conditions

(Temperature: -20ºC to +50ºC, relative humidity: 10% to 95%).

Investigators gave the investigational product to the patient explaining in detail how to

use it and showing them a demonstration video. In addition, patients could read the

instructions for use included in the device box.

4.7. Identification of data to be recorded in the CRF

The Case Report Form (CRF) for this study is a printed document, which was designed

to collect and transmit to the sponsor / CRO all the information required in the protocol

for each subject of the study.

In the CRF, patients were identified solely with their randomization code and no

information that might reveal the identity of the patient was collected.

The data recorded directly in the CRF (considering it as a source document) are the

results of the VAS pain intensity, the quality of life questionnaire EQ-5D and

concomitant medication.

4.8. End of the study

End of the study was considered the day of the final visit of the last patient included.

5. SELECTION AND WITHDRAWAL OF PATIENTS

5.1.Definition of the study population

Subjects who fulfill all inclusion criteria and none of the exclusion criteria

which are listed below:

Inclusion Criteria

● Patients age equal to 18 years old or above

● Patient that meet the following criteria:


Page:14/45

o Acute or Chronic pain

o Moderate or severe pain intensity. The assessment of baseline pain

intensity should be taken after a minimum of 4 hours after the last dose

of regular analgesic.

o Pain caused by musculoskeletal disease of any etiology except bone

fracture.

Exclusion Criteria

● Pain caused by bone fracture

● Patients in analgesic treatment with opioid derivatives included in the group of

strong opioids, drugs of the third step according to the pain ladder of the World

Health Organization (WHO): Morphine, Oxycodone, Oxycodone-Naloxone,

Fentanyl, Hydromorphone, Tapentadol, and Buprenorphine.

● Injuries involving hospitalization or surgery for treatment in the area that has the

pain.

● Any contraindication for use of electrical stimulation, including history of

epilepsy, cardiac arrhythmias, pacemaker or other implantable programmable

device.

● Pregnant women or women of childbearing potential not using effective

contraception (Complete abstinence from sex, surgical sterilization (tubal

ligation), implanted or injectable hormonal contraceptives and oral

contraceptives are considered effective contraception). This reliable

contraception must be maintained throughout their participation in the study.

● Participation in another clinical trial in the three months preceding the study.

● Lack of will or inability to comply with the procedures of clinical trials.

Criteria for withdrawal.

The investigator could remove a patient from the study if they considered that the

patient could no longer meet all the requirements thereof or if any of the procedures was

possibly harmful to the patient. The data already gathered about the retired patients is

retained and used for analysis, but no new data for the study after the withdrawal was

collected.


Page:15/45

6. STATISTICS

6.1. Statistical methodology

Descriptive study of the variables

Quantitative variables were expressed as mean, median, standard deviation, confidence

interval 95% and the minimum and maximum values. This description was made for the

total sample and for each of the study groups.

The qualitative variables were presented in tabular form including absolute and relative

frequencies for both treatment groups and the global population.

Comparative study between groups

The homogeneity of the population at baseline with respect to demographic variables,

medical history and other clinical parameters was analyzed at baseline. For quantitative

variables t-student comparisons took place between the two groups of the study

(placebo and experimental). The qualitative variables were analyzed by a homogeneity

test based on the Chi-square distribution when it was possible and by Fisher exact test

values otherwise.

The evolution of these variables was analyzed using a linear mixed model with the

following factors for efficacy analysis: dependent variable (VAS results after

application) inter-subject factor (treatment group), co-variable (VAS results before

application) and random variable (subjects).

This model was used for other variables: dependent variable ( increase of VAS results,

number of daily use of device), inter-subject factor (treatment group) and random

variable (subjects).

All comparative analysis was done considering all population and after that, the two

strata (acute and chronic pain) were compared against each other.

The level of significance used in all statistics test was alpha =0,05

Statically analysis was performed with SPSS 21.0 computer software.

7. RESULTS

102 patients have been included in this study. 51 patients suffered from chronic pain


Page:16/45

and 52 patients suffered from acute pain.

16 patients were withdrawn due to different causes (withdrawal of consent, non-

compliance with the protocol, compliance with same exclusion criteria....), so 86

patients have been analysed in this study. 38 patients suffered from chronic pain and 48

patients suffered from acute pain.

Table 1 shows the distribution of patients by treatment group.

Table 1. Distribution of patients according to the type of pain Pain

Total Acute Chronic

Treatment Experimental 29 20 49

Placebo 19 18 37

Total 48 38 86

7.1. Demographic variables

The collected demographic variables are age and sex.

7.1.1. Age

Table 2 shows the patient’s age per treatment group.

No statistically significant differences were found when comparing the age of the study

groups (experimental and placebo) in the total population. The strata analysis shows

that there are no differences between placebo and experimental groups. So, the study

population was homogeneous in relation to the age.

Table 2. Age (mean and SD) and P between group in each stratum and total population

Pain Treatment Mean Standard Deviation

N P

Acute Experimental 45.93 12.66 29

0.54 Placebo 48.42 15.16 19

Chronic Experimental 48.70 11.45 20

0.13 Placebo 54.61 12.10 18

Total study

population

Experimental 47.06 12.13 49 0.12

Placebo 51.43 13.92 37

7.1.2. Sex

The distribution by sex in both groups is homogeneous (table 3) since no significant


Page:17/45

difference has been found between treatment groups.

Table 3. Number of men and women in each treatment group

Sex P

Men Women

Treatment

Experimental Number 13 36

0.551 % inside group 26.5% 73.5%

Placebo Number 12 25

% inside group 32.4% 67.6%

Total Number 25 61


7.2. Clinical variables

The distribution of patients related to the type of pain (acute or chronic) as well as the

study group (experimental and placebo) in which they were randomized is shown in

table 1.

According to the clinical variables measurement at baseline, 45.3% of the study

population suffered moderate pain while 54.7% suffered severe pain (table 4).

The distribution of the intensity of pain into treatment groups is homogeneous since no

significant differences between them were found.

Table 4. Distribution of patients according to the intensity of pain: Moderate and severe

Intensity of pain Total Moderate Severe

Treatment Experimental

Number 21 28

0.593


Placebo Number 18 19


Total Number 39 47


The distribution of patients based on the type of pathology that they presented as well as

the study group in which they were randomized, are shown in tables 5 (acute pain

group) and 6 (chronic pain group).


Page:18/45

Table 5. Type of pathology in acute pain stratum

Treatment Total

Experimental Placebo

Chondromalacia patella 1 0 1

Muscle contracture 4 3 7

Sprain 0 2 2

Multiple contusions 1 1 2

Worsening arthrosis 3 7 10

Carpal tunnel syndrome 2 0 2

Subacromial Syndrome 1 1 2

Acute tendinopathy 17 5 22

Table 6. Type of pathology in chronic pain stratum

Treatment Total


Arthrosis 7 7 14

Kyphoscoliosis 1 0 1

Muscle Contracture 2 1 3

Herniated disc 1 2 3

Poliomyelitis sequelae 0 1 1

Carpal tunnel syndrome 0 1 1

Myofascial Syndrome 6 4 10

Tendinopathy 2 2 4

The distribution of patients according to the location of the pain presented by the

subjects as well as the study group in which they were randomized is shown in tables 6

(acute pain) and 7 (chronic pain).

Table 6. Distribution of patients according to the location of the acute pain

Treatment Total


Cervical spine 2 3 5

Dorsal column 3 2 5

Lumbar spine 2 3 5

Shoulder 4 3 7

Elbow 8 1 9

Wrist 3 2 5

Hand 1 0 1

Knee 3 4 7

Ankle 0 1 1

Foot 2 0 2


Page:19/45

Table 7. Distribution of patients according to the location of the chronic pain

Treatment

Total Experimental Placebo

Generalized 1 2 3

Vertebral column 2 1 3

Cervical spine 4 0 4

Dorsal column 4 2 6

Lumbar spine 2 6 8

Shoulder 1 2 3

Elbow 1 0 1

Wrist 0 1 1

Hand 0 1 1

Knee 5 3 8

7.3. Efficacy analysis. Visual analogue scale (VAS)

7.3.1. Baseline

The analysis of VAS score at baseline shows that no statistically significant differences

among treatment groups were found (table 8) when we analyse the total study

population. The same result was obtained when we compare the results of the VAS

score between experimental and placebo groups in the acute and chronic pain strata

respectively (tables 9 and 10).

Therefore, we can say that the study population was homogeneous in terms of the VAS

score variable at baseline. This means that the treatment groups can be compared related

to VAS score variable with each other throughout the study.

Table 8. Mean and standard deviation of the baseline VAS score for total study population

Treatment N Mean SD P

VAS Experimental 49 6.735 1.1691

0.233 Placebo 37 6.417 1.2716

Table 9. Mean and standard deviation of the baseline VAS score for acute pain stratum


VAS Experimental 29 6.693 1.0351

0.071 Placebo 19 6.112 1.1119


Page:20/45

Table 10. Mean and standard deviation of the baseline VAS for chronic pain stratum


VAS Experimental 20 6,795 1,3667

0,901 Placebo 18 6,739 1,3789

7.3.2. Comparing the VAS score between treatment groups

In order to compare the VAS score among treatment groups, we have analysed the

differences between the VAS score before and after use. Firstly, we have calculated

these differences for total study population and then we have done the same analysis for

acute and chronic pain strata, respectively. Finally, we have compared the results of the

calculated differences between experimental and placebo groups.

Total study population

In general, a decrease of VAS score has been found after using the medical device,

taking the VAS score before use as a reference. This decrease is observed in the

experimental and placebo groups.

However, when we compare the reduction of the VAS score between treatment groups

(experimental and placebo) we find that the decrease in the VAS score in the

experimental group (1.0 ± 1.3) is statistically greater (p<0.001) than in the placebo

group (0.4 ± 0.7) (figure 2).


Page:21/45

Figure 2. The VAS score before and after using the device for experimental and placebo groups taking in account the

total study population

Therefore, we can conclude that the efficacy of the handheld TENS pen in relieving

general musculoskeletal pain have been shown

Acute pain stratum

The analysis of the VAS score before and after use in the acute pain stratum shows a

similar behaviour to that experienced by the total study population. After using the

experimental device, patients felt statistically significant (p<0,044) pain relief compared

with the placebo. So, experimental and placebo groups experienced a decrease of 1.1 ±

1.4 and 0.6 ± 0.9, respectively, in the VAS score (Figure 3) in the acute pain stratum.

Error bars


Page:22/45

Figure 3. Acute pain stratum.VAS score for experimental and placebo groups before and after using the device.


acute musculoskeletal pain have been shown

Chronic pain stratum

From analysis of the VAS score decrease in chronic pain stratum, (figure 4) a

statistically significant decrease (p<0.01) in the VAS score in the experimental group

(0.8 ± 1.2) in relation to the placebo group (0.2 ± 0.5) can be seen.


chronic musculoskeletal pain have been shown

Error barrs:


Page:23/45

Figure 4. Chronic pain stratum.VAS score for experimental and placebo groups before and after using the device

Table 11 displays that the VAS scores showed by the acute pain stratum, before and

after the use of the device, were 4.9 ± 2.1 and 3.8 ± 2.4, respectively, in the

experimental group. While the placebo group experienced VAS scores from 6.2 ± 1.9 to

5.5 ±1.8 before and after the device use, respectively.

As table 11 also shows, the chronic pain stratum experienced VAS scores from 6.6 ±1.8

to 5.7 ± 2.1, before and after using the experimental device, respectively, while the VAS

scores in the placebo group were 4.9 ± 2.0 and 4.7 ± 2.5 before and after using the

device, respectively.

Error Bars


Page:24/45

Table 11. Mean and standard deviation of VAS score before and after use in total study population and in

acute and chronic pain groups

Pain Treatment VAS Before VAS After

P

Acute

Experimental Mean 4.9 3.8

0.044* SD 2.1 2.4

Placebo Mean 6.2 5.5

SD 1.9 1.8

Chronic


0.01* SD 1.8 2.1


SD 2.0 2.0

Total

Study

Population


0.001* SD 2.1 2.5


SD 2.1 2.0 *Statistically significant (p<0.05)

7.3.3. Temporary evolution of the daily VAS scores

In order to study the temporary evolution of the VAS scores, we have calculated the

daily average differences of VAS scores before and after use for the study period (28

days). Then, we have compared the daily calculated values among experimental and

placebo groups for total study population as well as for acute pain and chronic pain

strata.


a) Daily decrease of VAS score

The results show a daily decrease of VAS score after the device use.

From comparison of the study groups, we can observe that the daily VAS score

reduction in the experimental group is significantly greater (p<0.001) than in the

placebo group.

Therefore, the efficacy of the device was maintained for 28 days (length of the study)

(figure 5) when considering the total study population.


Page:25/45

Figure 5. Daily decrease of VAS scores after device use. Total population.

As figure 5 shows, the daily VAS score decrease remains constant throughout the study

(p=0.682) in the experimental group. Therefore, the use of the experimental device

relieves the pain in the same manner every day for 28 days independent of pain type.

b) Daily decrease of VAS score before the experimental device use.

Regarding the VAS scores before the experimental device use, figure 6 shows that

there is a significant decrease of this score over the days (p <0.001). In this way, the

VAS score on the first and 28 days was 6.2 ± 1.8 and 5.2 ± 2.1 points on baseline and

28 days respectively.

Treatment

Day

Error bars


Page:26/45

Figure 6. Temporary evolution of the VAS score obtained before the use of the experimental device. Total

population

So, the handheld TENS pen efficacy remains constant over a 28-day period in

alleviating general musculoskeletal pain. Furthermore, the pain relief is the same for

each day of the treatment.

Acute pain stratum


Figure 7 shows the daily decrease of the VAS score in the acute pain stratum.

Results show that the decrease of the VAS score in the experimental group is

statistically higher than that obtained in the placebo group for days 1 and 5 and shows a

tendency to a greater decrease (p <0.1) on days 17, 18, 23, 24, 25, 26, 27 and 28.

As can be seen in figure 7, the decrease of the VAS score in the experimental group

does not remain constant throughout the study (p <0.030) showing greater decrease on

days 2, 5, 6, 8, 9, 10, 11, 22, 24, 25, 26 and 28 (p <0.05) with respect to the first day of

the study. Therefore, the decrease in pain intensity resulting from the use of the

experimental device is greater in the days after the first use for acute pain.

Error bars


Page:27/45

Figure 7. Daily decrease of VAS scores after device use. Acute pain group

b) Daily decrease of VAS score before the experimental device use

The temporary evolution of the VAS score before the use of the experimental device

shows that there was a significant decrease throughout the study (p <0.001). In this way,

the VAS score was 5.9 ± 1.5 and 4.7 ± 2.2 points at baseline and at 28 days,

respectively (figure 8).

Figure 8. Temporary evolution of the VAS score obtained before the use of the experimental device. Acute pain

stratum

Treatment

Day

Error bars

Error bars


Page:28/45

Chronic pain group


Results show that there is a decrease in the VAS score after using the device by the

chronic pain stratum. When comparing the daily decrease in the VAS score after

application of the device between the placebo and the experimental groups, we observed

that this is statistically higher (p<0.05) in the experimental group than that obtained in

the placebo group for 1, 2, 3, 4, 14 and 28 days and shows a tendency to a greater

decrease (p <0.1) on days 7, 8, 9, 10, 11, 12 and 25 (figure 9).

Referring to figure 9, we can see that the VAS score decrease experienced by the

experimental group is not constant (p <0.001). We observe a daily minor decrease in

VAS scores compared to the first day (p<0.05) except on days 2, 7 and 14. Therefore,

the decrease in the intensity of pain after the use of experimental device is lower on the

days after the first day in the chronic pain stratum.

Figure 9. Daily decrease of VAS scores after device use. Chronic pain group

Treatment

Error bars:

Day


Page:29/45


Figure 10 shows that the temporary evolution of the VAS scores before the use of the

experimental device does not change significantly during the study.

Figure 10. Temporary evolution of the VAS score obtained before the use of the experimental device. Chronic pain

group.

7.3.4. First use

FIRST DAY OF USE

Comparison of the VAS score before and after the first use of the device on the

first day

From comparative analysis between the VAS score before and after the first use of the

experimental device significant differences were found (p<0.05). However, these

differences are not significant in the placebo group. This fact is observed when we

consider the total study population or each stratum separately (table 12).

However, when we compare the changes in VAS scores obtained from the first use

between the experimental and the placebo groups no significant differences are

observed (table 12). This is applicable to the total study population as well as to acute

and chronic pain strata.

Error bars


Page:30/45

Table 12. VAS scores before and after the first use

Pain Treatment VAS Before VAS After P Time

P Time x

Treatment

Acute

Experimental Mean 5.9 5.4 0.009

0.072 SD 1.6 1.8

Placebo Mean 6.0 5.8 0.259

SD 1.5 1.6

Chronic


0.408 SD 2.0 2.3


SD 1.8 1.8

Total

study

population


0.079 SD 1.8 2.0


SD 1.6 1.7

FIRST DAILY USE

Comparison of daily VAS scores before and after the first daily use of the device.

Table 13 shows the results of the global VAS scores before and after the daily first use

of the device.

As table 13 shows, significant differences (p<0.05) have been found between the

experimental and placebo groups with respect to the global decrease of the VAS score

after the first daily use. These differences appear considering the total population and

considering any of the strata.

Significant differences (p<0,05) have been found between the moment before and after

using the device for the first daily use in all study groups but there are greater

differences in experimental groups with respect to the placebo.


Page:31/45

Table 13. VAS scores before and after the daily first use.

Pain Treatment VAS Before

VAS After

P Time

P Time x

Treatment

Acute


0.001

0.001 SD 2.1 2.2


0.001 SD 2.1 2.0

Chronic


0.001

0.001 SD 2.0 2.2


0.001 SD 2.0 2.0

Total

study

population


0.001

0.001 SD 2.1 2.3


0.001 SD 2.1 2.0

Temporary evolution of the VAS scores after first daily use



The analysis of the temporary evolution of VAS scores decrease after the first daily use

is shown in figure 11. This graph illustrates that the decrease of the VAS score in the

experimental group is statistically higher than that obtained in the placebo group on

most days and, therefore, the experimental device decreases pain intensity in the first

application of the day more effectively than the placebo device in the majority of the 28

days of use.


Page:32/45

Figure 11. Decrease in the VAS score of the daily first use. Total study population

The results for VAS scores decrease after the first daily use of the experimental device

indicate that they are constant and, therefore the decrease in pain intensity resulting

from the use of the experimental device is equal throughout the 28 days of application

for the total study population.


On observation of the temporary evolution of the VAS score before the first use of the

experimental device, it does not change for 28 days (figure 12).

Figure 12. Temporary evolution of the VAS score obtained before the first use of the experimental device. Total

study population

Error Bars

Day

Error Bars


Page:33/45

Acute pain stratum


The comparative results between the daily VAS scores after using the experimental and

placebo device do not show significant differences in any days. Therefore, we cannot

say that the experimental device reduces the intensity of pain in the first application of

the day more effectively than the placebo device during the 28 days of application

(figure 13) for the acute pain stratum.

As figure 13 shows, the VAS scores decrease after using the experimental device

remains constant for 28 days.

Figure 13. Decrease in the VAS score of the daily first use. Acute pain stratum


From the temporary evolution of the VAS score before the first daily use of the

experimental device, we can support that this variable does not change throughout the

28 days (figure 14).

Error bars

Day


Page:34/45

Figure 14. Temporary evolution of the VAS score obtained before the first use of the experimental device. Acute

pain stratum



The results of the VAS score decrease after the first daily use of the experimental device

are statistically higher (p<0.05) than those obtained after using the placebo device.

Therefore, the experimental device decreases pain intensity in the first use of the day

more effectively than the placebo device in the majority of the 28 days of application

(figure 15).

As figure 15 illustrates, the decrease of the VAS scores are maintained constantly

during the study for the experimental group. Therefore, the decrease in pain intensity

resulting from the application of the experimental device is the same throughout the 28

days of use in the chronic pain stratum.

Error bars


Page:35/45

Figure 15. Decrease in the VAS score of the daily first use. Chronic pain stratum


Regarding the temporary evolution of VAS scores before the first use of the

experimental device, we have observed that there are no modifications of this score with

the passage of days (figure 16).

Figure 16. Temporary evolution of the VAS score obtained before the first use of the experimental device. Chronic

pain stratum

Day

Error bars

Error bars


Page:36/45

7.4. Daily use of the device

Table 14 shows the average number of days that the patients used the device in acute and

chronic strata as well as in total study population.

Table 14. Number of days in which the device was used for acute and chronic strata. Mean and standard deviation.

Pain Treatment Mean SD P Treatment

Acute Experimental 3.68 2.248

0.64 Placebo 3.84 3.304

Chronic Experimental 4.60 4.121

0.56 Placebo 3.84 2.836

Total

study

population

Experimental 4.05 3.156

0.73 Placebo 3.84 3.040

The comparative analysis of this variable shows that there is no statistically significant

difference between the study groups (experimental and placebo) nor between the days

of use of the device.

Patients used the experimental device the same number of times per day than those who

used the placebo device.

There are no variations in the number of times that the subjects used the device during

28 days. So, during the study period, the experimental and placebo devices were used

the same number of times.

We can see the same results for the total population and for acute and chronic pain strata

(figures 17, 18 and 19).


Page:37/45

Figure 17. Use per day of the device. Total population

Figure 18. Use per day of the device. Acute pain stratum

Treatment

Error bars

Treatment

Error bars


Page:38/45

Figure 19. Use per day of the device. Chronic pain stratum

7.5. Use of rescue medication.

Before starting the study, 42.9% of the subjects who used the experimental treatment

(acute pain 27.6% and chronic pain 65.0%) and 29.7% who used the placebo treatment

(acute pain 15.8% and chronic pain 44.4%) used rescue medication (Table 15).

There were no significant differences between the experimental and placebo groups at

baseline in relation to the use of rescue medication for the study population overall as

well as for each stratum.

Table 15. Use of rescue medication

Pain Treatment Baseline Follow-up P

Time x Treatment

Acute Experimental 27.6% 3.6% 0.012

Placebo 15.8% 10.5%

Chronic Experimental 65.0% 65.0% 0.318

Placebo 44.4% 33.3%*

Total study

population

Experimental 42.9% 29.2% 0.858

Placebo 29.7% 21.6%

Treatment

Error bars


Page:39/45

As table 15 shows, rescue medication was used in 29.2% of subjects in the experimental

group (acute pain 3.6% and chronic pain 65.0%) and 21.6% of those who were in the

placebo group (acute pain 10.5% and chronic pain 33.3%) (Total p = 0.431; acute pain p

= 0.338; chronic pain p <0.05). The percentage of subjects suffering from chronic pain

that used rescue medication in the experimental group was significantly (p <0.05)

higher than in the placebo group. However, this difference was not appreciated in the

group of patients with acute pain or in the general group.

The percentage of subjects with acute pain that used rescue medication during the study

decreased significantly with respect to the baseline when they used the experimental

device compared to the placebo device. However, patients with chronic pain did not

reduce the use of rescue medication.

7.6. Quality of life questionnaire.

The quality of life was measured by the EQ-5D questionnaire which was answered at

baseline and at the final visit.

EQ-5D is a generic instrument for measuring health-related quality of life that can be

used in both relatively healthy individuals (general population) and in groups of patients

with different pathologies. The individual themselves value their health, first in levels of

gravity (descriptive system) and then in a visual analogue scale of more general

evaluation. A third element of the EQ-5D is the index of social values that is obtained

for each health status (question) generated by the questionnaire. So, the index of social

values is the evaluation of health status.

7.6.1. Assessment of health status by the variable: pain / discomfort level.

The percentage of subjects who responded positively to each level of the pain /

discomfort (none, moderate and extreme) at baseline and at the final visit was analysed

for total study population and for acute and chronic pain strata separately.

Total population

The temporary evolution for this variable showed these results (table 16):


Page:40/45

- Both the experimental and placebo groups experienced an increase in the

percentage of subjects who answered with the level "none" and this rise was the

same for the two groups.

- There was a decrease in the percentage of subjects who answered with the level

"moderate" in the placebo group but the percentage was constant in the

experimental group. No significant differences were observed in this different

evolution (p <0.09).

- There was a decrease in the percentage of subjects who answered with the level

"extreme" in both groups. Significant differences were observed in this decrease

being the decrease occurring in the experimental group (p <0.003) greater.-

Table 16. pain/discomfort level for total population

Pain/discomfort level Treatment Initial Final P Time x Treatment

None Experimental 0% 30.4%

0.318 Placebo 2.7% 30.0%

Moderate Experimental 55.1% 60.9%

0.09 Placebo 70.3% 50.0%

Extreme Experimental 44.9% 8.7%

0.003 Placebo 27.0% 20%

Acute pain stratum

We have analysed the temporary evolution of pain/discomfort level for acute pain

stratum and we have seen (table 17):

- The percentage of subjects who answered with the level "none" increased in

both groups (experimental and placebo). This rise is the same for both groups.

- The percentage of subjects who answered with the level "moderate" decreased in

both groups. Significant differences between groups were observed being the

decrease occurring in the placebo group (p <0.04) greater than in experimental

group.

- The percentage of subjects who answered with the level "extreme" decreased in

the experimental group. However the percentage did not change in the placebo

group. Significant differences were observed in this different evolution (p

<0.001).


Page:41/45

Table 17. pain/discomfort level for acute pain stratum

Pain/discomfort level Treatment Initial Final P Time x Treatment


0.107 Placebo 5.3% 43.8%

Moderate Experimental 69.0% 55.6%

0.04 Placebo 78.9% 37.5%

Extreme Experimental 31.0% 7.4%

0.001 Placebo 15.8% 18.8%


We have analysed the temporary evolution of pain/discomfort level for chronic pain

stratum (table 18):

- The percentage of subjects who answered with the level "none" increased in

both groups (experimental and placebo). This rise is the same for both groups.

- The percentage of subjects who answered with the level "moderate" incresed in

the experimental group while this percentage was constant in the placebo group.

Significant differences were observed in this different evolution (p <0.023).

- The percentage of subjects who answered with the level "extreme" decreased in

both groups. The decrease occurring in the experimental group was significantly

greater than in the placebo group (p <0.003).

Table 18. pain/discomfort level for chronic pain stratum

Pain/discomfort level Treatment Initial Final P

Time x Treatment


0.788 Placebo 0% 14.3%

Moderate Experimental 35% 68.4%

0.023 Placebo 61.1% 64.3%

Extreme Experimental 65% 10.5%

0.003 Placebo 38.9% 21.4%

7.6.2. Evaluation of health status: Index of social values.

The index of social values goes from 0 to 100 being 100 the best health status.

The analysis of the social values index significantly increased in placebo (P<0.001) and

in experimental (p<0.002) groups considering the total population.


Page:42/45

The comparative between groups shows that there are not significant differences.

However, a tendency to greater increase for the experimental group (p=0.064) was

observed (figure 20).

Figure 20. Index of social values used for the evaluation of health status. Total population *p<0.05= differences between baseline and final visit $p<0.1 =differences between groups when evolution is analysed

Results of social values index for acute and chronic pain status are shown in figure 21

and 22 respectively.

The social values index significantly increased in patients who suffer acute pain both in

the experimental and placebo groups (p<0.001 and p<0.014, respectively). However, the

comparative of the temporary evolution of social indexes does not show differences

between the placebo and experimental groups.

As figure 22 illustrates, patients with chronic pain experienced a significant increase of

the social values index when they used the experimental device (p<0.001). In addition,

significant differences were found between the experimental and placebo groups due to

the significant increases (p<0.042) in social values index experienced by the

experimental group.

* *

$

Error bars


Page:43/45

Table 19 shows the average of social value indexes and p values.

Figure 21. Index of social values used for the evaluation of health status. Acute pain stratum *p<0.05= differences between baseline and final visit

Figure 22. Index of social values used for the evaluation of health status. Chronic pain stratum *p<0.05= differences between baseline and final visit # p<0.05 =differences between groups when evolution is analysed

* *

* #

Error bars

Error bars


Page:44/45

Table 19. Mean and SD of social values index

Pain Treatment Time Mean SD P Time

P Time x

Treatment

Acute

Experimental Baseline 52.3 20.1

0.001

0.416

Final 75.1 19.8

Placebo Baseline 55.7 20.6

0.014 Final 71.5 26.7

Chronic


0.001

0.042

Final 56.7 22.4


0.068 Final 62.6 26.1

Total study

population


0.001

0.064

Final 67.5 22.6


0.002 Final 67.2 26.3

8. TOLERANCE AND SAFETY

The safety of the investigational medical device was assessed by recording the adverse

events (AEs) during the study, that is, from baseline to final visit.

Signs and symptoms corresponding to side effects related or not related to the medical

device were collected and described to document the tolerance to the device.

Only two patients suffered an adverse event related to the experimental device. These

events were described as erythema on the skin surface after the device application. The

symptoms disappeared after the patients stopped using the device.

Therefore, we can say that the experimental device is safe and was well tolerated by

97.67% of the study population.


Page:45/45

9. CONCLUSIONS

The efficacy of the handheld TENS pen, used on demand for 28 days, has been

evaluated both for the relief of general musculoskeletal origin pain as well as for acute

and chronic pain of the same origin in particular, and it has been found that:

The following conclusions were drawn from the data evaluation and analysis of this

study:

1. The handheld TENS pen is effective in relieving general musculoskeletal pain

2. The handheld TENS pen is effective in relieving acute musculoskeletal pain

3. The handheld TENS pen is effective in relieving chronic musculoskeletal pain

4. The handheld TENS pen efficacy remains constant over a 28-day period in alleviating

general musculoskeletal pain. Furthermore, the pain relief is the same for each day of

the treatment.

5. The handheld TENS pen reduces the acute and chronic musculoskeletal pain intensity

daily as well as the general and acute musculoskeletal pain that patients feel each day

before using the device.

6. The handheld TENS pen produces greater relief of acute musculoskeletal pain on

most days compared to the first day of use.

7. The first application of the treatment provides pain-relieving effects in patients with

general musculoskeletal pain and especially for patients with both acute and chronic

pain. However, the effect of the first application has not reached the level of “statistical

significance”.

8. During treatment, the first daily application is effective for general musculoskeletal

pain relief as well as for the relief of acute and chronic pain in particular.

9. The handheld TENS pen improves the quality of life of the subjects reducing the

perception of pain in the case of general musculoskeletal pain and especially for patients

with both acute and chronic pain and increasing the subjective evaluation of health

status in individuals with chronic pain.


Page:46/45

10. The use of the handheld TENS pen is safe and well tolerated

11. The handheld TENS pen reduces the use of rescue medication for patients with

acute pain

12. 83% of individuals with chronic pain who used the handheld TENS pen felt that

their pain had gone from severe to moderate or none.

An Investigation into the Hypoalgesic Effects ofTranscutaneous Piezoelectric Current onExperimentally Induced Thermal Stimuli inHealthy Participantsner_349 242..248

Anthony Blenkinship, BSc*, Alex E. Benham, MSc*†, Osama Tashani, PhD*†,and Mark I. Johnson, PhD*†

Objectives: To investigate the effects of transcutaneous piezoelectric currents on experimentally induced thermal pain in healthyhuman participants.

Materials and Methods: A repeated measure cross-over study recorded sensory detection and pain thresholds to contactthermal stimuli during active and placebo (no current) transcutaneous piezoelectric current in 15 pain-free healthy humanvolunteers. Active transcutaneous piezoelectric current (6 mA) was delivered as 35 high voltage single rectangular pulses (1 Hz) atthe LI4 (Hegu) acupuncture point.

Results: Repeated measures ANOVA found that active and placebo transcutaneous piezoelectric current elevated thresholds forwarm sensation, heat pain, and cold sensation. However, there were no statistically significant effects for active piezoelectriccurrent compared with placebo for any outcome measure.

Conclusions: Reductions in experimentally induced pain were not due to piezoelectric currents per se. These findings challengeclaims about the efficacy of transcutaneous piezoelectric currents for pain relief. A clinical trial is needed.

Keywords: Nontherapeutic human experimentation, pain threshold, PainGone pen, transcutaneous electric nerve stimulation,transcutaneous piezoelectric current

Conflict of Interest: M. Johnson received a one-off consultancy payment on behalf of his institution for writing a critical review ofa medical device for the same company, PainGone. The medical device was called PainDoctor. He has delivered occasionalworkshops on TENS that have been sponsored by TENS and pharmaceutical companies. The other authors reported no conflicts ofinterest.

INTRODUCTION

Transcutaneous electrical nerve stimulation (TENS) is used through-out the world to manage painful conditions (1). A variety of TENS-like devices, which differ in design to a standard TENS device, areavailable to the general public without prescription. A review ofTENS-like devices found that there was very little good qualityresearch on putative mechanisms, efficacy, and effectiveness andthat manufacturers overstate the efficacy (2). Transcutaneous piezo-electric current devices are TENS-like and categorized as Class IIamedical devices (e.g. PainGone (3), Piezo No Needle AcupuncturePen (4)). It is claimed that piezoelectric currents can relieve pain, yetthere has been minimal research on the efficacy and/or mechanismof action (5–7).

Transcutaneous piezoelectric current devices are shaped likeoversized pens without batteries, lead wires, or self-adhering elec-trodes. A single point electrode is often used to deliver a highvoltage single rectangular pulsed piezoelectric current generatedby mechanically forcing two crystals (piezoelectric elements)together by a plunger, achieved by “clicking” a button on the device.

Each pulse is claimed to be 15,000 V and of short pulse duration,resulting in an electrical current “shock” of small amplitude (6 mA)through the skin. Manufacturers recommend that 30–40 “clicks” ofstimulation at a rate of one to two pulses per second should beadministered to areas of pain or acupuncture points to relieve painassociated with minor ailments, arthritis, back pain, headache, andsports injuries (3,4).

Evidence for effectiveness for pain relief is limited to one smallscale randomized controlled clinical trial without a placebo control,

Address correspondence to: Mark I. Johnson, PhD, Faculty of Health, Leeds Met-ropolitan University, Civic Quarter, Leeds LS1 3HE, UK. Email: [email protected]

* Faculty of Health, Leeds Metropolitan University, Leeds, UK; and† Leeds Pallium Research Group, http://www.leeds.ac.uk/palliumSource of financial support: Leeds Metropolitan University.

For more information on author guidelines, an explanation of our peer reviewprocess, and conflict of interest informed consent policies, please go to http://www.wiley.com/bw/submit.asp?ref=1094-7159&site=1

Neuromodulation: Technology at the Neural Interface

Received: September 30, 2010 Accepted: January 27, 2011

(onlinelibrary.wiley.com) DOI: 10.1111/j.1525-1403.2011.00349.x

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www.neuromodulationjournal.com Neuromodulation 2011; 14: 242–248© 2011 International Neuromodulation Society

which concluded that piezoelectric stimulation lowered pain inten-sity and reduced medication use for participants with acute neckand back pain (5). Case series, some of which are not published inpeer-reviewed journals, also claim that piezoelectric stimulationreduces back and neck pain (8), cancer pain (6), chronic musculosk-eletal pain (9), and lateral epicondylitis (10). As these observationslack a placebo comparison, it is possible that the pain relievingeffects were produced by the act of administering the piezoelectriccurrent rather than the piezoelectric current itself.

It is claimed that pens that deliver transcutaneous piezoelectriccurrent work on similar principles to TENS, although descriptions ofthe mechanism of action are very general, such as closing the paingate and releasing endorphins (5–7). One experimental study foundthat piezoelectric currents reduced nociceptive flexion reflexes (RIIIreflex), with maximal inhibition of the reflex occurring within thefirst 4 min after stimulation (11). To our knowledge, no other experi-mental studies have been conducted. Studies assessing hypoalgesiain healthy human participants exposed to experimentally inducedpain are commonly used as precursors to clinical trials and are usefulin determining the efficacy, appropriate technique, and optimal set-tings for analgesics including TENS (12).

The aim of this study was to investigate the hypoalgesic effects oftranscutaneous piezoelectric currents delivered using a PainGonepen on experimentally induced thermal pain in healthy human par-ticipants. Thermal stimuli were chosen because they have a closeassociation with activity in small diameter A-delta and C-fibre affer-ents (13).

METHODS

A repeated measure cross-over study was designed to measureexperimentally induced thermal sensory detection and pain thresh-olds during transcutaneous piezoelectric current (PainGone) andplacebo transcutaneous piezoelectric current (no current) in pain-free healthy human volunteers. Informed consent was obtainedfrom all participants, and the study was approved by the ResearchEthics Sub-Committee of Leeds Metropolitan University.

Participants, Recruitment, and SelectionPain-free unpaid healthy human volunteers were recruited byadvertisements placed throughout the university. Volunteers

expressing interest were invited to attend a pre-study familiariza-tion session, where they were given a participant information sheetand briefed about the nature of the study, background to TENS, andthe procedure for inducing thermal pain. Volunteers were screenedagainst eligibility criteria: 18 years or older, no previous use of TENS,and not contraindicated to TENS and/or the experimental proce-dure in line with current professional standards (14). These contrain-dications included any existing medical condition such asperipheral vascular abnormalities, hypertension and hypotension,peripheral neuropathies, and recent trauma. TENS action dependson normally functioning nerves in the skin, so normal skin sensationwas an inclusion criterion. Volunteers who were taking any medica-tion or who were likely to take any medication during the period ofstudy were excluded. Volunteers meeting these eligibility criteriawere invited to take part in the study which was scheduled noearlier than 48 hours after the familiarization session.

ProcedureEach participant took part in two experimental sessions conductedin a physiology laboratory and separated by a 24-hour “washout”period. Participants signed written consent before the start of eachexperiment and were reminded that they could withdraw at anytime without any reason. Participants were seated throughout theexperiment with their non-dominant forearm resting on a side tableand instructions delivered verbally, using a series of cue cards.

Participants, received active transcutaneous piezoelectric currentin one experiment and placebo transcutaneous piezoelectriccurrent (no current) in the other. Unrestricted randomization wasused to determine the order of the interventions and operational-ized by rolling a dice. Active and placebo devices were identical in allaspects of appearance. Sensory detection and pain thresholds tothermal stimuli were measured at baseline and 1 min and 11 minafter active or placebo tanscutaneous piezoelectric current (Fig. 1).

Transcutaneous Piezoelectric Current InterventionsTranscutaneous piezoelectric current was administered within a2-min intervention period using a PainGone device (MediDirectInternational, Nottingham, UK) and following advice given in theuser manual that transcutaneous piezoelectric current should beadministered at the site of pain or at an acupuncture point related to

Baseline

Threshold measures Threshold measures Threshold measuresIntervention

1 min post

intervention

11 min post

intervention

cold

sensation

threshold

cold pain

threshold

warm

sensation

threshold

heat pain

threshold

0 min 10 min 12 min13 min

23 min 33 min

Figure 1. Experimental procedure.

243HYPOALGESIC EFFECTS OF PIEZOELECTRIC CURRENTS


the pain by administering 30–40 clicks of the device. Interventionswere administered by the participant, who placed the transcutane-ous piezoelectric current device onto the skin at the LI4 (Hegu)acupuncture point, which had been marked with ink before thestart of the experiment by an acupuncturist. LI4 (Hegu) is located onthe hand between the first and second metacarpal bones and is apoint that is commonly used to reduce pain (Fig. 2). Participantswere instructed to“Place the stimulator pen so that it is touching thesurface of the skin. You should feel the device touch the skin but itshould not be pressed so hard that it is uncomfortable.” Participantswere instructed to deliver 35 stimuli (clicks of the device) and theywatched a digital stop clock to ensure that the rate of clicks wasmaintained at one click every 1 sec (i.e., 1 Hz). The investigatorcounted the number of clicks aloud.

Active transcutaneous piezoelectric current devices deliveredhigh voltage (15,000 V) single rectangular pulsed piezoelectric cur-rents that had short pulse durations (widths) resulting in a 6 mA/clickbeing delivered through the skin (3). It was not possible to alter theintensity of stimulation because current amplitude was fixed in thedevice. Placebo transcutaneous piezoelectric current was adminis-tered using a sham device that had been modified by the manufac-turers so that there was no current output. These sham devices wereidentical in appearance, and it was not possible to distinguish themfrom active devices when clicked. Participants had been told in thefamiliarization session that there were different types of TENSdevices and some produced a sensation and others did not. Theywere informed that during the experiment they may or may not feelany sensation. Participants were instructed not to discuss anyaspect of the intervention with the investigator, and if they had anyquestions they should tell the investigator, who would get the inde-pendent person to resolve the issue. No requests of this nature weremade. They were also told that they should not tell the investigatorwhether they feel a sensation from the device.

Sensory Detection and Pain Thresholds MeasurementsA TSA-II Neurosensory Analyser (Medoc Ltd, Israel), which uses thePeltier principle to generate thermal stimuli, was used to measurethresholds for cold sensation, cold pain, warm sensation, and heatpain, in that order (Fig. 1). The method of ascending limits was usedfor heat stimuli and method of descending limits for cold stimuli. An

average of three measurements was taken for each threshold beforemoving on to the next threshold to be measured. A run of threerepeats of each threshold measurement to the upper and lowerlimits (50.5°C and 0°C, respectively) would take a total of 9 min30 sec, so a 10-min run time was used. Thermal stimuli for all mea-surements began at 32°C and either increased (warm sensation andheat pain) or decreased (cold sensation and cold pain) at a rate of0.5°C/sec. A 30 ¥ 30 mm thermode probe was used to deliver stimuliand pressed onto the surface of the skin on the lateral aspect of theforearm 5 cm proximal to the first wrist crease. This position corre-sponds to the C6 dermatome, which is segmentally related to theLI4 acupuncture point.

Data AnalysisWe used a within-subject model and conducted 3x2 factorialrepeated measures ANOVAs on data. Factors were Time (Threelevels: baseline and post intervention at 1 min and 11 min) andIntervention (two levels: active and placebo). The order (sequence)of receiving active or placebo transcutaneous piezoelectric currentwas used as a between-subject factor (two levels). If Mauchly’s testof Sphericity was not assumed, then a Greenhouse-Geisser correc-tion was used. Alpha was set at 0.05, beta at 0.2 (i.e., power of 0.8),and adjustment made for multiple comparisons using the Bonfer-roni correction.

RESULTSCharacteristics of the Study GroupFifteen healthy volunteers took part in the familiarization sessionand all completed both experimental sessions (ten males, mean age= 22.26 years, range 19 to 26). Six participants received active trans-cutaneous piezoelectric current during the first visit (Fig. 3).

Cold Sensation Detection ThresholdSphericity could not be assumed for Time and Time ¥ Intervention.Significant effects were detected for Time (p = 0.037) but not Inter-vention (p = 0.396) or Time ¥ Intervention interaction (p = 0.697).There were no significant effects for interactions between Interven-tion ¥ Sequence (p = 0.744), or Time ¥ Sequence (p = 0.550). Pairwisecomparisons for Time detected a significant elevation in cold detec-tion threshold (i.e., a reduction in temperature) relative to baselineat 1 min and 11 min irrespective of active and placebo transcutane-ous piezoelectric current (p = 0.094 and p = 0.12, respectively,Table 1). There was no significant change in cold detection thresh-old between 1 min to 11 min (p = 1.00)

Hot Sensation Detection ThresholdSphericity could not be assumed for Time. Significant effects weredetected for Time (p < 0.001) but not Intervention (p = 0.732) or Time¥ Intervention interaction (p = 0.924). There were significant effectsfor interactions between Intervention ¥ Sequence (p = 0.009) butnot for Time ¥ Sequence (p = 0.208). Pairwise comparisons for Timedetected a significant elevation in heat detection thresholds relativeto baseline at 1 min and 11 min irrespective of active and placebotranscutaneous piezoelectric current (p = 0.001 and p = 0.001,respectively). There was also a significant rise in heat detectionthreshold between 1 min to 11 min (p = 0.023).

Cold Pain ThresholdSphericity could not be assumed for Time. There were no significanteffects detected for Time (p = 0.102), Intervention (p = 0.688), or

Figure 2. Experimental set-up.

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Time ¥ Intervention interaction (p = 0.195). There were no significanteffects for interactions between Intervention ¥ Sequence(p = 0.700) or Time ¥ Sequence (p = 0.412).

Heat Pain ThresholdSphericity could not be assumed for Time or Time ¥ Intervention.Significant effects were detected for Time (p < 0.001) but not Inter-vention (p = 0.400) or Time ¥ Intervention interaction (p = 0.806).There were significant effects for interactions between Intervention¥ Sequence (p = 0.018), but not for Time ¥ Sequence (p = 0.822).

Pairwise comparisons for Time detected a significant rise in heatpain threshold relative to baseline at 1 min and 11 min irrespectiveof active or placebo transcutaneous piezoelectric current (p = 0.001and p < 0.001, respectively). There was also a significant rise in heatpain threshold between 1 min to 11 min (p = 0.027).

DISCUSSION

This study found that 35 pulses (clicks) of piezoelectric currentadministered to LI4 (Hegu) did not affect thermal detection thresh-

Assessed for eligibility (n=15)

Randomised (n=15)

Excluded Not meeting inclusion criteria (n=0)Refusal to participate (n=0)Other reasons (n=0)

Allocated to sequence Active followed by Placebo (n=6)

Received allocated intervention (n=6)

Did not receive allocated intervention (n=0)

Allocated to sequencePlacebo followed by Active (n=9)

Received allocated intervention (n=9)

Did not receive allocated intervention (n=0)

Analysed (n=6)

Excluded from analysis (n=0)

Lost to follow-up (n=0)

Discontinued intervention (n=0)

Analysed (n=9)

Excluded from analysis (n=0)

Lost to follow-up (n=0)

Discontinued intervention (n=0)

Figure 3. Flow of participants through study.

Table 1. Mean (SD) detection thresholds for experimentally induced cold and heat stimuli before and 1 min and 11 min after active and placebo (no current)transcutaneous piezoelectric current.

Baseline 1 min post-intervention 11 min post-intervention

Cold detection thresholdActive 30.76 (0.48) 29.77 (1.81) 30.01 (0.92)Placebo 30.59 (0.79) 29.44 (2.92) 29.76 (1.22)

Heat detection thresholdActive 33.55 (0.49) 35.78 (2.50) 36.63 (2.98)Placebo 33.82 (1.00) 36.11 (2.17) 36.96 (2.64)

Cold pain thresholdActive 18.06 (8.70) 18.61 (9.10) 19.14 (7.39)Placebo 16.52 (8.29) 18.60 (7.33) 19.43 (6.94)

Heat pain thresholdActive 41.12 (3.30) 42.46 (3.87) 43.08 (3.70)Placebo 42.11 (3.84) 43.62 (3.36) 43.91 (3.37)

Thermal stimuli started at 32°C.



olds for sensation or pain in the same dermatome. There wereincreases in detection thresholds for cold, warmth, and heat pain forboth active and placebo transcutaneous piezoelectric current rela-tive to baseline. However, these changes were not due to piezoelec-tric currents per se because there were no differences betweenactive and placebo interventions. Neither active nor placebo trans-cutaneous piezoelectric current changed cold pain threshold rela-tive to baseline.

A systematic search of PubMed identified one experimental studyby Danzinger et al. (11) that found strong and long lasting inhibitoryafter-effects on lower limb nociceptive RIII flexion reflexes in 24healthy women following 2 min of piezoelectric currents. Piezoelec-tric currents were administered as high-voltage, low-charge, low-intensity, and low-frequency rectangular pulses by a piezoelectricceramic device similar to that used in our study. Stimulation wasapplied both segmentally and heterotopically for 2 min. Long-lasting inhibitory after-effects on the RIII reflex, used as a correlate ofpain, were observed when compared with placebo (no current).Maximal inhibition of the reflex occurred up to 4 min after stimula-tion and had returned to control levels within 14 min for segmentalstimulation and 40 min for heterosegmental stimulation. Non-noxious high frequency TENS inhibited the RIII reflex only during thestimulation period itself whereas higher intensity low frequencyTENS produced more prolonged poststimulation effects.

In our study, we applied active and placebo stimulation seg-mentally and found elevations in detection thresholds for warmth,cold and heat pain relative to baseline in a similar time course toDanzinger et al. (11). We observed elevations in heat pain thresh-old during placebo transcutaneous piezoelectric current, whereasDanziger et al. did not observe changes in the RIII reflex duringsham transcutaneous piezoelectric current. We used a shorterstimulation period of 35 sec (i.e., 35 clicks at one pulses persecond) compared with 2 min used by Dazinger et al. and we mea-sured response to thermal stimuli rather than electrical stimuli.However, the most likely explanation for discrepancies betweenthe results was the large placebo response in our study comparedwith no placebo response in the RIII reflex in the study by Dazingeret al.

In post-experimental debriefing, participants described activetranscutaneous piezoelectric current stimulation at LI4 as anuncomfortable “pin prick” that was not overtly noxious and occa-sionally radiated toward the thumb and index finger. These obser-vations suggest high and low threshold cutaneous afferents (e.g.,A-delta and A-beta, respectively) were stimulated during activetranscutaneous piezoelectric current. Electrophysiologic evidencesuggests that activation of A-beta afferents generates a short lastingsegmental inhibition of second order centrally transmitting noci-ceptor cells (15,16). By selectively activating A-beta afferents, non-noxious TENS creates a strong non-painful paraesthesia at the site ofpain, which masks pain during stimulation but is short lived afterthe stimulator has been switched off (1). Activation of A-delta affer-ents has been shown to generate stronger inhibition of secondorder centrally transmitting nociceptor cells lasting up to two hourspoststimulation (17). In addition, higher intensity stimulation acti-vates descending pain inhibitory pathways and diffuse noxiousinhibitory controls (18–20). Our study suggests that transcutaneouspiezoelectric current did not affect central or peripheral processingof A-delta and C-fibre afferent activity resulting from thermalstimuli. Future studies using other experimental pain modalitiessuch as pressure algometry, submaximal tourniquet effort test,intramuscular saline injection, and delayed onset muscle sorenesswould be useful.

It is claimed that transcutaneous piezoelectric current acts as ahyperstimulant (2,3). If so, it will activate high threshold peripheralafferents and initiate acupuncture-like or even counter-irritationmechanisms. Mild erythema was noted post-stimulation in a smallnumber of participants, and Dazinger et al. (11) reported “goose-flesh” over the site of stimulation immediately after stimulation fol-lowed by local skin reactions akin to neurogenic inflammation andtactile alloynia. Whether these contribute to putative actions oftranscutaneous piezoelectric current is unknown, so follow-upstudies are needed.

Study LimitationsMethodological aspects of the study need to be considered anexplanation for the lack of effect (i.e., a false negative finding). It ispossible that the active transcutaneous piezoelectric current wasdelivered at an insufficient dose (i.e., too few clicks or too few acu-puncture points) and/or inadequate technique (i.e., inappropriatesite of application, inappropriate electrical parameters). However,we followed the manufacturer’s instructions on use (3). The studywas designed mirroring previous studies that have detected effectsbetween groups using similar methodologies (i.e., a TSA-II Neuro-sensory Analyser) and sample sizes, so we have no reason to doubtthe internal sensitivity of our procedures (21). It is possible that ourstudy was too short in duration and that the onset of hypoalgesiaassociate active transcutaneous piezoelectric currents was delayedin onset or cumulative over a series of treatment sessions.

Clinical ImplicationsThe findings of our experimental study cannot be extrapolated tothe clinical population. Nevertheless, there is widespread availabil-ity of transcutaneous piezoelectric current for pain relief, so a briefreview of clinical research would be useful for practitioners. We onlyfound one randomized controlled trial of piezoelectric stimulationof acupuncture points for acute back and neck pain on 18 patients,which concluded that piezoelectric stimulation lowered pain inten-sity by 20%, reduced the use of medication, and shortened the timeto recovery when compared with patients receiving no stimulation(5). Patients received a total of 40 stimulations at each of five visits.A Piezo DX device (ITO Corporation, Japan) was used with a ground-ing pole held in the ipsilateral hand for leg point stimulation or inthe ipsilateral antecubital fossa for hand stimulation. At each visitpatients received a total of 40 stimulations (back pain = 5 bilateralstimulations on GB 34 and GB 39, and bilateral ten stimulations onBL 60; neck pain = 10 bilateral stimulations at SI 4 and BL 58). Inaddition, each patient received two to ten stimulations on Ah Shipoints in the local area of pain. Only nine patients receiving activestimulation and six patients receiving sham stimulation entereddata analysis. There was no difference in the change in global painintensity scores from day 1 to day 21 of the study until the scores ofnon-responders were removed from the dataset. To our knowledgethere are no other controlled trials of transcutaneous piezoelectriccurrent.

All published case series on transcutaneous piezoelectric currentreport benefit. Shapiro had previously reported successful use ofpiezoelectric current in three patients with acute back and neckpain (8), and Niemtzow et al. reported successful use of piezoelec-tric current in three patients with various carcinomas (6). A confer-ence communication by Ivanova-Stoilova and Howells (9)described 36 patients with chronic musculoskeletal pain whoreported good pain relief with transcutaneous piezoelectric

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current delivered using PainGone. An unpublished manuscript of acase series of 25 patients reported that 76% of patients with lateralepicondylitis reported good to excellent pain relief immediatelyafter administering 25 pulses of transcutaneous piezoelectriccurrent once a day for 3–5 days over or just above the most painfularea (10). None of these studies used a placebo control group, so itis possible that the pain relieving effects were produced by the actof administering the piezoelectric current rather than the piezo-electric current itself.

CONCLUSION

In conclusion, transcutaneous piezoelectric current administered atLI4 did not alter thermal thresholds for sensation or pain over andabove that observed with placebo (no current) transcutaneouspiezoelectric current. Our study should serve as a catalyst for furtherexperimental and clinical research.

Acknowledgements

The authors wish to express gratitude to Dr. Ghazala Tabasam forsupport in the delivery of this study. This study was funded by LeedsMetropolitan University.

Authorship Statement

All authors designed the study. Mr. Blenkinship conducted the studywith the technical support provided by Dr. Benham. All authorscontributed to data analysis. Professor Johnson prepared the firstdraft of the manuscript. All authors approved the final manuscript.

How to Cite this Article:Blenkinship A., Benham A.E., Tashani O., Johnson M.I.2011. An Investigation into the Hypoalgesic Effects ofTranscutaneous Piezoelectric Current on Experimen-tally Induced Thermal Stimuli in Healthy Participants.Neuromodulation 2011; 14: 242–248

REFERENCES

1. Johnson MI. Transcutaneous electrical nerve stimulation and acupuncture. In: Stan-nard C, Kalso E, Ballantyne J, eds. Evidence-based chronic pain management. London:Wiley-Blackwell Publishing, 2010:337–365.

2. Johnson MI. Transcutaneous electrical nerve stimulation (TENS) and TENS-likedevices. Do they provide pain relief? Pain Reviews 2001;8:121–128.

3. Paingone. Fast, effective drug-free pain relief. 2010. Available from: http://www.paingone.com/(accessed April 26, 2010).

4. MasterFormula.net. Piezo no needle Acupuncture Pen. 2010. Available from: http://www.masterformula.net/piezo_pen.htm(accessed April 26, 2010).

5. Shapiro D. Piezoelectric stimulation for back and neck pain: a randomized con-trolled trial. Acupunct Med 2004;15:27–30.

6. Niemtzow R, Ong R, Johnstone P. Piezoelectric stimulation technique of acupunc-ture points: clinical application. Acupunct Med 2000;12:31–32.

7. White PF, Li S, Chiu JW. Electroanalgesia: its role in acute and chronic pain manage-ment. Anesth Analg 2001;92:505–513.

8. Shapiro D.Piezoelectric stimulation of acupuncture points for the treatment of backand neck pain: a discussion of 3 case reports. Acupunct Med 2001;13:11–12.

9. Ivanova-Stoilova T, Howells D. The usefulness of PainGone pain killing pen for self-treatment of chronic musculoskeletal pain—a pilot study. The Pain Society AnnualScientific Meeting 2002;abstract:104.

10. Asbjorn O. Treatment of tennis elbow with transcutaneous nerve stimulation (TNS).2000. Available from: http://www.medial.cz/data/files/medial/download/klinicke_studie/medidirect/paingone_1.pdf (accessed April 26, 2010).

11. Danziger N, Rozenberg S, Bourgeois P, Charpentier G, Willer JC. Depressive effects ofsegmental and heterotopic application of transcutaneous electrical nerve stimula-tion and piezo-electric current on lower limb nociceptive flexion reflex in humansubjects. Arch Phys Med Rehabil 1998;79:191–200.

12. Staahl C, Drewes AM. Experimental human pain models: a review of standardisedmethods for preclinical testing of analgesics. Basic Clin Pharmacol Toxicol2004;95:97–111.

13. Fowler CJ, Sitzoglou K, Ali Z, Halonen P. The conduction velocities of peripheralnerve fibres conveying sensations of warming and cooling. J Neurol Neurosurg Psy-chiatry 1988;51:1164–1170.

14. Chartered Society of Physiotherapy (CSP). Guidance for the Clinical Use of Electro-physical Agents. London: Chartered Society of Physiotherapy, 2006.

15. DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA. Effectiveness of transcuta-neous electrical nerve stimulation for treatment of hyperalgesia and pain. CurrRheumatol Rep 2008;10:492–499.

16. Garrison DW, Foreman RD. Decreased activity of spontaneous and noxiouslyevoked dorsal horn cells during transcutaneous electrical nerve stimulation (TENS).Pain 1994;58:309–315.

17. Sandkühler J, Chen JG, Cheng G. Low-frequency stimulation of afferent A delta-fibers induces long-term depression at primary afferent synapses with substantiagelatinosa neurons in the rat. J Neurosci 1997;17:6483–6491.

18. DeSantana JM, da Silva LF, de Resende MA, Sluka KA. Transcutaneous electricalnerve stimulation at both high and low frequencies activates ventrolateral periaq-ueductal grey to decrease mechanical hyperalgesia in arthritic rats. Neuroscience2009;163:1233–1241.

19. Sandkuhler J. Long-lasting analgesia following TENS and acupuncture: spinalmechanisms beyond gate control. Devor M, Rowbotham MC, Wiesenfeld-Hallin Z,eds. 9th World Congress on Pain: Progress in Pain Research and Management. Austria:IASP Press, 2000:359–369.

20. Morton C, Du H, Xiao H, Maisch B, Zimmermann M. Inhibition of nociceptiveresponses of lumbar dorsal horn neurones by remote noxious afferent stimulationin the cat. Pain 1988;34:75–83.

21. Watson PJ, Latif RK, Rowbotham DJ. Ethnic differences in thermal pain responses: acomparison of South Asian and White British healthy males. Pain 2005;118:194–200.

COMMENTARY

Transcutaneus Electrical Neurostimulation for acute and chronic painhas been a disappointment for a number of years in terms of under-standing potential indicatons and demonstrating efficacy. Placeboeffects in pain management are quite common, and yet, significanthealth care funds are expended annually on products and deviceswithout evidence-based backing or scientific support. This article givesperspective to this issue.

Richard Weiner, MDDallas Neurosurgical Associates

Dallas, TX USA

***It has long been known that most therapeutic modalities, particularlythe ones in the area of neuromodulation, have a significant “placebo”component—perhaps having to do with a distraction or anticipationexperienced by their subjects. Transcutaneous electrical nerve stimu-lation (TENS), acupuncture and electro-acupuncture are some of thosemodalities where the clinical effects are hard to quantify and the treat-ment outcomes are rather unpredictable.

Here, the authors of the study decided to test piezoelectric currentsthat are used for suppression of pain—usually through self-administered stimulation to the painful areas or to the acupuncturepoints—in terms of change in perception thresholds, and comparedeffects of these currents with placebo stimulation. They found no dif-ference whatsoever between simple skin contact of pseudo-deviceand electrical current from commercially available piezoelectric appli-cator. One would wonder if the pressure with placebo device produceslocal effects similar to the electrical current from real device—but evenif this is true, the findings of this study raise a major doubt on clinicalefficacy of piezoelectric stimulation.

I congratulate the authors on well-designed and carefully imple-mented study that is both simple and informative—and hope that



they follow up on their own recommendations and perform furtherexperimental and clinical research with this modality to clarify mecha-nism of analgesic action (if any) or clearly show it uselessness forchronic pain patients.

Konstantin V. Slavin, MDProfessor

Neurological Surgery—CSUniversity of Illinois at Chicago

Chicago, IL USA

Comments not included in the Early View version of this paper.

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104. THE USEFULNESS OF PAIN GONE® PAIN KILLING PEN FOR SELF-TREATMENT OF CHRONIC MUSCULO-SKELETAL PAIN – A PILOT TRIAL

Dr. Tzvetanka Ivanova-Stoilova, MD, PhD, FRCA, Consultant Anaesthetist, Royal Gwent Hospital, Newport, S.Wales

Dr. David Howells, MB, FRCA, SpR anaesthetics, Royal Gwent Hospital, Newport, S.Wales

Introduction: Pain Gone® is a new piece of equipment designed for self-treatment of pain from the body surface, originally developed in Denmark and available in the UK since 1999. It is a plastic unit the size of a big pen. Electronics and microcrystals are placed inside and on pressure on the top of the pen a high voltage (15,000V), low frequency 1-2 Hz and low potency (0,000006 amp) electrical current is delivered to the treatment area. The therapeutic zaps can be applied through light clothing. A single unit can last for 2-3 years. To date we are not aware of published studies on the device.

Aim: To evaluate the usefulness of the new device - Pain Gone® painkilling pen in alleviating chronic musculo-skeletal pain by self-treatment.

Materials and Methods: We enrolled 36 patients with chronic musculo-skeletal pain (shoulder, knee, elbow, low back pain, cocydynia, cervical spondylosis, trigger point syndrome pain). They were instructed to apply 10-15 zaps with the pen around the painful body area. This could be repeated several times a day until satisfactory pain relief is achieved or sustained. The pen was used for a period of 14 days. Its usefulness was evaluated by comparing the pre- and post-treatment variables: VAS, mobility, quality of life, amount of pain relief medication. The patients were asked to assess its convenience to use at home and while travelling, express their overall satisfaction and willingness to try to get it again by filling a questionnaire at the end of the trial.

Results: 61% (22 patients) were satisfied and 39% (14 patients) were dissatisfied with the device. The two outcome groups of patients who did not differ in their pre-treatment VAS scores, mobility or quality of life. The patients that benefited from the pen reported a mean reduction of pain severity by 33% (ranging from 20-85%); 10 patients (45%) had improvement in mobility, 8 patients (36%) reduced their analgesic medication. They all found the device easy to use, convenient for travel and were willing to try it again. 6 months later 73% of them had purchased the pen and were using it as a rescue treatment. Patients dissatisfied with the device did not obtain pain relief. 4 Patients (28%) found it difficult to use, but 5 patients (35%) wished to try it again. 6 months later none of them had been using the pen.

Discussion: The mechanism of the analgesic action of Pain Gone might be similar to neuromodulatory effect of TENS. Pain Gone® does not require application of gels, pads and wires and there are no on-going costs. Our trial with the device showed that it is well accepted by patients and it is a useful adjuvant for medication-free self-treatment of chronic pain. A placebo effect cannot be ruled out.

Conclusions: More studies are needed to elucidate the full potential of the device and types of pain most likely to respond to treatment with Pain Gone®. A double blind randomised controlled trial appears to be justified.

Acknowledgement: We thank UK Care Products for the supply of the pens for the trial.

The Usefulness of PainGone® Pain Killing Pen for Self Treatment of Musculoskeletal pain – A Pilot Trial

Dr. Tzvetanka Ivanova-Stoilova, MD, PhD, FRCA, Consultant Anaesthetist, Dr. David Howells, MB, FRCA, SpR anaesthetics, Royal Gwent Hospital, Newport, South Wales

Aim

• To evaluate the usefulness of the new device Pain Gone® painkilling pen in alleviating chronic musculo-skeletal pain by self-treatment

Introduction

• Originally designed in Denmark Pain Gone® painkilling pen is a new piece of equipment for self treatment of pain from the body surface.

• It is a sealed plastic unit the size of a big pen inside which are electronics and crystals.

• A high voltage 15,000 volt low frequency 1-2 Hz and low potency 6.10

-6 amp electrical current is delivered on

pressure applied to the top of the pen.

• The device can be applied on bare skin or through light clothing.

• A single unit can last for 2-3 years / 100,000 zaps.

• No pads, gels batteries or on-going costs.

Materials and Methods

• Included 36 patients with chronic musculo-skeletal pain – shoulder, knee, elbow, low back pain, coccydynia, cervical spondylosis, trigger point syndrome.

• Excluded: pregnant, epileptic with pacemaker, senile dementia, skin infection and acute onset of new symptoms.

• Assessment by consultant.

• Device demonstrated to patient.

• Pre-treatment assessment of VAS, mobility, quality of life and medication.

• Device loaned for 14 day home trial.

• Post-treatment assessment form completed by patient - VAS, mobility, ease of use and convenience of use while travelling.

• 6 months follow up.

Acknowledgement

• We thank UK Care Products for the supply of the pens for the trial.

Protocol

• First, 3 zaps to both Li 4 acupuncture points.

• Painful area to be zapped 5 – 10 times.

• Session to be repeated as frequently as necessary at 5 minute intervals.

Results

• VAS – mean of 7.3

• Quality of life - good: 47% (17) poor: 53% (19)

• Mobility good: 47% (17) poor: 52% (19) Patients’ Evaluation

6 months Follow-up

• 16 patients (73%) of the satisfied had purchased a pen and are using it as rescue treatment.

• None of the initially dissatisfied had purchased or used it again.

Discussion

• Mechanism of action of PainGone® is believed to be similar to TENS.

• We consider the possibility of “needless” acupuncture effect as well.

• A placebo effect cannot be riled out.

• To our knowledge this is the first clinical trial in the UK.

• Price of a single unit on the UK market: £59 - £69.

Conclusion

• PainGone® pain killing pen is a safe, easy to use, medication free pain controlling device which can be used for self-treatment.

• A randomised controlled trial seems to be justified to confirm the findings of this study.

Reference: 1. Alan King, Non-invasive acupuncture for everyone. King’s Medical 2000, p63.

Satisfied with PainGone® Dissatisfied with PainGone 61% (22 patients) 39% (14 patients) VAS reduction by mean No reduction of VAS. of 33% (20 – 85%). In 5 (35%) pain is worse. Easy to use. Not easy 4 (28%). Convenient. Not convenient 1 (7%). Less medication. Same medication. Would like to buy. Would like to try again 5 (35%).

Pain Reviews 2001; 8: 121–158

© Arnold 2001 10.1191/0968130201pr182ra

IntroductionTranscutaneous electrical nerve stimulation(TENS) is used by health care professionalsthroughout the world to provide pain relief for awide range of conditions, including postoperativepain, labour pain and chronic pain. During

TENS, electrical currents are generated by astimulating device and delivered across the intactsurface of the skin via conducting pads calledelectrodes (Figure 1). The popularity of TENShas grown because it is noninvasive, easy toadminister and has few side effects or drug inter-actions. There is no potential for toxicity or over-dose and patients can administer TENSthemselves at home and titrate the dosage oftreatment as required. When compared withlong-term drug therapy, TENS treatment is con-siderably cheaper.1–3

Recently, systematic reviews have challenged

Address for correspondence: Mark I Johnson, School ofHealth Sciences, Faculty of Health and Environment, LeedsMetropolitan University, Calverley Street, Leeds LS1 3HE,UK. E-mail [email protected]

Transcutaneous Electrical NerveStimulation (TENS) and TENS-like devices: do they providepain relief?Mark I JohnsonSchool of Health Sciences, Faculty of Health and Environment,Leeds Metropolitan University, UK

The term ‘transcutaneous electrical nerve stimulation’ (TENS) is synonymous with a standard TENSdevice. Increasingly, nonstandard TENS-like devices are being marketed to health care professionals forpain relief. These include: interferential current therapy, microcurrent electrical therapy, high-voltagepulsed (galvanic) currents, TENS-pens, transcranial electrical stimulation and Limoge currents, Codetron,transcutaneous spinal electroanalgesia, action potential simulation, and H-wave therapy. This review eval-uates the effectiveness of TENS and TENS-like devices for pain relief, to inform health care profession-als about device selection. The results from systematic reviews suggest that TENS is not effective forpostoperative pain and labour pain, although volatile evaluation models may partly explain the �ndings.Evidence is inconclusive for chronic pain. Health care professionals should not dismiss the use of TENSfor any condition until the issues in clinical trial design and review methodology have been resolved. Thereis limited experimental evidence available for most TENS-like devices. Claims by manufacturers aboutthe speci�city and extent of effects produced using TENS-like devices are overstated and could probablybe achieved by using a standard TENS device or a microcurrent electrical therapy device. When makingdecisions about device selection, health care professionals should consider the physiological intention ofcurrents and whether this can be achieved by using particular devices. Clinical trials that examine the rel-ative effectiveness of TENS-like devices with a standard TENS device are desperately needed.

122 MI Johnson

Pain Reviews 2001; 8: 121–158

claims that TENS is clinically effective.Bandolier, the journal for evidence-based healthcare that uses the �ndings of systematic reviewsto provide ‘clinical bottom lines’ states that:‘TENS is not effective in the relief of postopera-tive pain’4; ‘TENS does not alleviate labour painnor reduce the use of additional analgesics’5;‘There is a lack of evidence for the effectivenessof TENS [for chronic pain] at recommendedtreatment schedules’.6 Concerns about TENS’effectiveness have not reduced the variety ofTENS devices reaching the market, which seemto be fuelled in part by advances in electronictechnology and the need to gain a competitiveedge in the market place. The aim of this articleis to review critically the clinical effectiveness ofTENS and TENS-like devices for pain relief inorder to inform decisions about device selection.For the purpose of this article TENS-like devices

include any stimulating device that delivers elec-trical currents across the intact surface of the skinand whose generic name differs from TENS. Thiswill include interferential current therapy (IFT),microcurrent electrical therapy (MET), high-voltage pulsed (galvanic) currents (HVPC),TENS-pens (in particular, high-voltage TENS-pens), transcranial electrical stimulation (TCES,in particular Limoge currents), Codetron, tran-scutaneous spinal electroanalgesia (TSE), actionpotential simulation (APS), and H-wave therapy(HWT). This list is not exhaustive. The reviewwill not address the potential use of TENS-likedevices for nonpainful conditions, although ref-erence to these uses will be made where deemedappropriate.

Figure 1 A standard TENS device. An electrical pulse generator delivers currents via conducting electrodesattached to the intact surface of the skin. Traditionally, carbon rubber electrodes smeared with conducting geland attached to the skin using self-adhesive tape were used to deliver the electrical currents. Nowadays, self-adhesive electrodes are used (modi�ed from Figure 17.1 in: Johnson M. Transcutaneous electrical nervestimulation (TENS). In: Kitchen S ed. Electrotherapy: evidence-based practice. Edinburgh: ChurchillLivingstone, 2001: 259–862; with permission from Elsevier Science)

Ef�cacy of TENS and TENS-like devices in pain relief 123

Pain Reviews 2001; 8: 121–158

De� ning TENSIn broad terms TENS is anything that deliverselectricity across the intact surface of the skin toactivate underlying nerves. This would includethe delivery of electric shocks by electrogenic�sh, as was commonly used in early history, andthe harnessed and controlled delivery of currentswith speci�c characteristics as used in mostmodern-day TENS devices. A broad de�nition ofTENS would not take account of the electricalcharacteristics of the currents (i.e., the outputcharacteristics or technical speci�cations of thedevice). However, in health care the term TENSis commonly used to describe currents deliveredby a ‘standard TENS device’ (Figure 1).

The standard TENS deviceStandard TENS devices are distinguished bytheir output characteristics. They usually deliverbiphasic pulsed currents in a repetitive mannerwith a pulse duration between 50 µs and 1000 µsand pulse frequencies between 1 and 250 pulsesper second (pps).1,2,7–9 Pulses are usually deliv-ered in a continuous pattern, although mostmodern-day devices have other patterns availablesuch as burst and modulation (Table 1, Figure 2).The technical speci�cations and output charac-

teristics of standard TENS devices vary betweenmanufacturers, as they attempt to achieveuniqueness and a competitive edge in the market-place. However, these variations are minor andprobably have limited impact on the physiologi-cal effects produced by the devices. As TENS isa technique-based intervention, outcome will bedictated by the appropriateness of TENS proce-dures used to deliver currents as determined bythe end-user. A number of factors need to beconsidered when determining a TENS procedure,including the characteristics of the electrical cur-rents selected by the user (i.e., the output char-acteristics), the application procedure (i.e.,electrode type and location) and the dosingregimen (Figure 3). The number of potentialTENS procedures is vast, even with a simpleTENS device, so it is important that the user hasbasic knowledge about the principles underpin-ning TENS techniques.

Principles of TENSThe purpose of TENS is to activate selectivelydifferent populations of nerve �bres in order toproduce particular physiological outcomes. The common types of TENS described in the literature are1,7,9:

Table 1 The technical speci�cations of a standard TENS device modi�ed from Table 1 in: Johnson MI. Acritical review of the analgesic effects of TENS-like devices. Phys Ther Rev 2001; 6: 153–7310)

Weight Dimensions 50–250 g

6 ´ 5 ´ 2 cm (small device) 12 ´ 9 ´ 4 cm (large device)

Cost £30–150Pulse waveform (usually �xed) Monophasic

Symmetrical biphasicAsymmetrical biphasic

Pulse amplitude (usually adjustable) 1–50 mA into a 1 k W loadPulse duration (sometimes �xed, sometimes adjustable) 10–1000 µs Pulse frequency (usually adjustable) 1–250 pps Pulse pattern Continuous and burst

Some devices have random pulse frequencySome devices have modulated pulse amplitudes, frequencies and/or duration

Channels 1 or 2 Batteries PP3 (9V), rechargeableAdditional features Timer

124 MI Johnson

Pain Reviews 2001; 8: 121–158

� Conventional TENS;� Intense TENS;� Acupuncture-like TENS (AL-TENS)

(Table 2).

These types of TENS have evolved fromknowledge about the ability of various nerve�bres to activate different analgesic mechanismsin the body. Evidence from axonal stimulationstudies in vitro suggests that excitability variesaccording to the characteristics of an externallyapplied electrical current. The different types ofTENS attempt to describe the most ef�cientcharacteristics of current to activate endogenousanalgesic mechanisms and they have been widelyaccepted in the health care profession.Unfortunately, the use of these ‘banner’ terms

oversimpli�es TENS techniques and this hasresulted in TENS literature that tends to focus onthe output characteristics of TENS devices ratherthan the physiological intention of the currents.Evidence suggests that the theoretical relation-ship between output characteristics and nerve�bre activation may break down in practiceowing to the nonhomogeneous nature of thetissue underlying the electrodes.11,12 It is impor-tant to clarify the physiological intention of dif-ferent types of TENS when delivered by astandard TENS device.

Conventional TENSThe purpose of conventional TENS is to acti-

vate selectively large diameter Ab �bres without

AMPLITUDE

HIGH

LOW

DURATION

SHORT LONG

FREQUENCY

HIGH (250pps) LOW (1pps)

PATTERN

CBM

On

Off4

F7

6

9

10 1

5

2

38

2

3

46

8

9

10 1

7 5

I4

D7

6

9

10 1

5

2

38

CONTINUOUS

FREQUENCY MODULATED

RANDOM PULSES

Figure 2

BURST

Figure 2 Common output characteristics on standard TENS devices (topographic view). Most devices allowthe amplitude and frequency of electrical pulses to be controlled by the end-user. Pulse duration and pulsepattern options are also available on some standard TENS devices: (pps: pulses per second; I: intensity; F:frequency; D: duration; C: continuous; B: burst; M: modulation) (modi�ed from Figure 17.1 in: Johnson M.Transcutaneous electrical nerve stimulation (TENS). In: Kitchen S ed. Electrotherapy: evidence-basedpractice. Edinburgh: Churchill Livingstone, 2001: 259–862; with permission from Elsevier Science)


Pain Reviews 2001; 8: 121–158

Figu

re 3

Var

iabl

es i

n�ue

ncin

g th

e w

ay i

n w

hich

TE

NS c

an b

e ad

min

iste

red.

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y pos

sibl

e co

mbi

natio

ns o

f T

EN

S p

aram

eter

s ca

n be

chos

en b

y th

e en

d-us

er

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seP

ulse

Pul

seE

lect

rod

eP

resc

ribe

dO

pen

freq

uen

cyin

ten

sity

pat

tern

Num

ber

Loca

tion

Tim

eFr

eque

ncy

As

muc

h as

you

like

1–25

0 pp

s1–

50 m

AC

ontin

uous

Pen

(po

int)

Site

of

pain

�S

econ

ds�

Per

day

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efor

e pa

inP

arae

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st2

elec

trod

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erve

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dle

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day

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g pa

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bare

ly p

erfc

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ando

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le c

hann

elA

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re p

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rs�

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wee

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forta

ble

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k)M

odul

ated

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ectr

odes

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ger

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rs�

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mon

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ong)

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ents

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nial

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odes

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126 MI Johnson

Pain Reviews 2001; 8: 121–158

Tab

le 2

TEN

S t

echn

ique

s th

at c

an b

e ac

hiev

ed u

sing

a s

tand

ard

TEN

S d

evic

e. T

he o

utput

(el

ectr

ical

) ch

arac

teri

stic

s id

enti�

ed f

or e

ach

TEN

S t

echn

ique

are

bas

ed o

n th

e st

reng

th a

nd d

urat

ion

of p

ulse

d cu

rren

ts n

eces

sary

to

gene

rate

an

actio

n pot

entia

l in

diff

eren

t ty

pes

of

axon

.7In

clin

ical

pra

ctic

e, p

atie

nts

and

pra

ctiti

oner

s us

e th

e se

nsat

ion

prod

uced

by

TEN

S t

o de

term

ine

the

appro

priat

e st

imul

atin

g ch

arac

ter-

istic

s (m

odi�

ed f

rom

Tab

le 2

in:

Joh

nson

MI.

A c

ritic

al r

evie

w o

f th

e an

alge

sic

effe

cts

of T

EN

S-li

ke d

evic

es.

Phys

Ther

Rev

200

1;

6:

15

3–7

31

0)

Purp

ose

ofTh

eore

tical

opt

imum

Sens

ory

expe

rienc

eEl

ectro

de p

ositi

onAn

alges

ic pr

o�le

Dur

atio

n of

Mec

hani

sm o

fcu

rrent

sou

tput

cha

ract

erist

icsdu

ring

stim

ulat

ion

treat

men

tan

alges

ic ac

tion

(des

ired

outc

ome)

Conv

entio

nal

Selec

tive

Hig

h fre

quen

cy/lo

wSt

rong

but

Site

of p

ain

Rapi

d on

set <

30m

inC

ontin

uous

lySe

gmen

tal

TENS

activ

atio

n of

inte

nsity

:co

mfo

rtabl

eDe

rmat

omal

afte

r sw

itch

onw

hen

in p

ainno

nnox

ious

cut

aneo

usAm

plitu

de =

low

elect

rical

Rapi

d of

fset <

30m

ins

affe

rent

s (e

.g. A

ßD

urat

ion

= 10

0–20

0µs

para

esth

esia

afte

r sw

itch

off

�bre

s fro

mFr

eque

ncy

= 10

–200

pps

with

min

imal

mec

hano

rece

ptor

s)Pa

ttern

= c

ontin

uous

mus

cleco

ntra

ctio

n

AL-T

ENS

Selec

tive

Low

frequ

ency

/hig

hSt

rong

but

Mot

or p

oint

/mus

cleDe

layed

ons

et >

30m

ins

~30

min

s/se

ssio

nEx

trase

gmen

tal

activ

atio

n of

inte

nsity

:co

mfo

rtabl

eat

site

of p

ain

afte

r sw

itch

onas

mus

cle fa

tigue

Segm

enta

lm

otor

effe

rent

s to

Ampl

itude

= h

igh

mus

cle tw

itche

sM

yoto

mal

Delay

ed o

ffset

>1

hm

ay o

ccur

gene

rate

a m

uscle

Dur

atio

n =

100–

200

µsaf

ter

switc

h of

ftw

itch

and

activ

ityFr

eque

ncy

= 2

bps

and

in n

onno

xiou

s m

uscle

100

pps

with

in b

urst

affe

rent

s (i.

e. G

IIIPa

ttern

= b

urst

�bre

s fro

mer

gore

cept

ors)

Inte

nse

TEN

SAc

tivat

ion

of n

oxio

usH

igh

frequ

ency

/hig

hH

ighe

st to

lerab

leSi

te o

f pai

n or

main

Rapi

d on

set <

30m

in~1

5 m

ins/

sess

ion

Perip

hera

l‘p

inpr

ick’ c

unta

neou

sin

tens

ity:

level

with

nerv

e bu

ndle

laf

ter

switc

h on

as p

atie

nts

Extra

segm

enta

laf

fere

nts

(i.e.

Aß

�bre

sAm

plitu

de =

hig

hm

inim

alpr

oxim

al to

delay

ed o

ffset

1h

expe

rienc

eSe

gmen

tal

from

noc

ipep

tors

Dur

atio

n =

1000

µsm

uscle

pain

afte

r sw

itch

off

disc

omfo

rtFr

eque

ncy

= 20

0pp

sco

ntra

ctio

nPa

ttern

= c

ontin

uous

bps:

burs

t per

sec

ond;

pps

: pul

ses

per

seco

nd


Pain Reviews 2001; 8: 121–158

concurrently activating small diameter Ad and C(pain-related) �bres or muscle efferents (Figure4).1,2,7,9,13 Theoretically, high-frequency (~10–250pps), low-intensity (nonpainful) currents with apulse duration between 100 µs and 200 µs wouldbe most ef�cient in selectively activating Ab�bres (Table 2).7 In practice, Ab afferent activityis recognized by the user reporting ‘strong butcomfortable’ nonpainful electrical paraesthesiabeneath the electrodes.14–16 Animal and humanstudies have demonstrated that TENS-inducedAb activity inhibits ongoing transmission of noci-ceptive information in the spinal cord and thatthis produces segmental analgesia with a rapidonset and offset16–19 The main determinant of Abactivity is suf�cient current amplitude; users areeasily trained to titrate amplitude so that it isstrong enough to generate a nonnoxious paraes-thesia (Ab activity) without frank pain (repre-

sentative of Ad or C �bre activity). It is claimedthat the magnitude of analgesia achieved duringconventional TENS is dependent in part on thepulse frequency, but the �ndings of experimentsin healthy people and patients are inconsis-tent.20–24 It has been suggested that patient pref-erences for different TENS settings whendelivering currents at a strong nonnoxious inten-sity may be for reasons of comfort rather thanputative differences in analgesic pro�les.15,25

Acupuncture-like TENSThe purpose of AL-TENS is to generate activ-

ity in small diameter muscle afferents (Ad orGroup III) arising from ergoreceptors thatrespond to muscle contraction.+>9,26 This isachieved indirectly by delivering currents at lowfrequencies (~1–10 Hz) at high but nonpainfulintensities over motor points in order to activate

Muscle

Aß - segmental

TENS electrodes TENS Currents

Anode Cathode

Ad

C

Conventional TENS

Figure 4

Proximal

Figure 4 The purpose of conventional TENS is to activate selectively nonnoxious cutaneous afferents (Ab)to initiate segmental antinociceptive mechanisms. Arrows indicate selective activation of nerve �bre transmit-ting impulses towards the central nervous system (modi�ed from Figure 17.1 in: Johnson M. Transcutaneouselectrical nerve stimulation (TENS). In: Kitchen S ed. Electrotherapy: evidence-based practice. Edinburgh:Churchill Livingstone, 2001: 259–862; with permission from Elsevier Science)

d

Ab segmental

128 MI Johnson

Pain Reviews 2001; 8: 121–158

Aa efferents resulting in a forceful but non-painful phasic muscle twitch27,28 The subsequentvolley of impulses from muscle afferents medi-ates an extrasegmental antinociceptive mecha-nism and the release of endogenous opioidpeptides in a manner similar to that suggested foracupuncture (Figure 5).7,29–32 Low frequencyburst patterns of pulse delivery were incorpo-rated in TENS devices because they were foundto be more comfortable than low-frequencysingle pulses in producing muscle twitches (Table2).28 It should be remembered that currents deliv-ered during AL-TENS will also activate Ab �bresduring their passage through the skin, leading tosegmental analgesia. AL-TENS has also beendescribed as the delivery of TENS to acupunc-ture points without reference being made to the

presence of muscle contractions. The use of theterm in this way is not entirely appropriate.33

Intense TENSThe purpose of intense TENS is to activate

small diameter Ad cutaneous afferents by deliv-ering TENS over peripheral nerves arising formthe site of pain at an intensity that is just tolera-ble to the patient (Figure 6).2,34–36 Currents areadministered at high frequencies (up to 150 pps)to prevent phasic muscle twitches that would betoo forceful for the patient to tolerate (Table 2).Cutaneous Ad afferent activity has been shownto block transmission of nociceptive informationin peripheral nerves and to activate extraseg-mental antinociceptive mechanisms.37–40 IntenseTENS will also activate Ab �bres, producing seg-

MUSCLE

Aû - segmental

TENS electrodes

CONTRACTION

GI

GIII - extrasegmental

Cathode Anode

MUSCLE

AL-TENS

Motor point

Figure 5

Proximal

TENS Currents

Figure 5 The purpose of AL-TENS is to activate selectively large diameter motor efferents to elicit anonpainful muscle twitch. This muscle twitch generates activity in ergoreceptors and small diameter muscleafferents to initiate extrasegmental antinociceptive mechanisms. In addition, Ab afferents are also likely tobecome active. Arrows indicate direction of relevant impulse information (modi�ed from Figure 17.1 in:Johnson M. Transcutaneous electrical nerve stimulation (TENS). In: Kitchen S ed. Electrotherapy: evidence-based practice. Edinburgh: Churchill Livingstone, 2001: 259–862; with permission from Elsevier Science)

Ab segmental

Aa


Pain Reviews 2001; 8: 121–158

mental antinociceptive effects. As intense TENSacts in part as a counterirritant, it can be deliv-ered only for a short time, but it may prove usefulpostoperatively and for minor surgical proce-dures and such as wound dressing and sutureremoval.13,41

In clinical practice in the UK, conventionalTENS is most commonly used. AL-TENS andintense TENS are used only in speci�c situations.Despite a large published literature on TENS,there is a lack of good quality and systematicexperimental work that has directly comparedthe clinical effectiveness and analgesic pro�les ofthese types of TENS.

The clinical effectiveness ofTENSWhen assessing TENS’ effectiveness one needs toisolate the effects due to the currents from theeffects associated with the act of giving the cur-rents. Many early TENS trials lacked appropri-ate controls and therefore changes observed intrials could have been due to patients’ expecta-tion that TENS would reduce pain. In addition,many early trials lacked randomization, leadingto the overestimation of treatment effects. Thiswas elegantly demonstrated by Carroll et al., whofound that 17/19 controlled clinical trials thatwere not randomized reported that TENS wasbene�cial for postoperative pain, whereas 15/17trials that were randomized reported that it wasnot.42 Recently, a number of systematic reviewsand meta-analyses on TENS have challenged the

Muscle

Aß - segmental

TENS electrodes TENS Currents

Anode Cathode

Ad - extrasegmental

C

Intense TENS

Figure 6

Proximal

Figure 6 The purpose of intense TENS is to activate noxious cutaneous afferents (Ad) to initiate extraseg-mental antinociceptive mechanisms and peripheral blockade of nociceptive impulses travelling in Ad �bres. Inaddition, Ab afferents are also likely to become active. Arrows indicate direction of relevant impulse informa-tion (modi�ed from Figure 17.1 in: Johnson M. Transcutaneous electrical nerve stimulation (TENS). In:Kitchen S ed. Electrotherapy: evidence-based practice. Edinburgh: Churchill Livingstone, 2001: 259–862;with permission from Elsevier Science)

Ab segmental

Ad extrasegmental

130 MI Johnson

Pain Reviews 2001; 8: 121–158

Table 3 A summary of systematic reviews and meta-analysis on the clinical effectiveness of TENS (modi�edfrom Table 17.4 in: Johnson M. Trancutaneous electrical nerve stimulation (TENS). In Kitchen S ed.Electrotherapy: evidence-based practice. Edinburgh: Churchill Livingstone, 2001: 259–862; with permissionfrom Elsevier Science)

Condition Existing reviews

Acute Pain Reeve et al., 199646: SRMixed conditions (dysmenorrheoa, dental, cervical, orofacial)TENS > control in 7/14 RCTsReviewers’ conclusion: evidence inconclusive – poor RCT methodology

Postoperative pain Reeve et al., 199646: SRTENS > control in 12/20 RCTsReviewers’ conclusion: evidence inconclusive – poor RCT methodologyCarroll et al., 199642: SRTENS > control in 2/17 RCTsReviewers’ conclusion: evidence of no effectBjordal et al., 2003.48 MATENS > sham for reducing analgesic consumption (MWD = 35.5%) Reviewers’ conclusion: evidence of effect – analgesic sparing

Labour Pain Reeve et al., 199646: SRTENS > control in 3/9 RCTsReviewers’ conclusion: evidence inconclusive – poor RCT methodologyCarroll et al., 199751: SRTENS > control in 3/8 RCTsReviewers’ conclusion: evidence of no effectCarroll et al., 199750: update of Carroll et al.,51: SRTENS > control in 3/10 RCTsReviewers’ conclusion: evidence of no effect

Chronic pain Reeve et al., 199646: SRMixed conditions (low back, pancreatitis, arthritis, angina)TENS > control in 9/20 RCTsReviewers’ conclusion: evidence inconclusive – poor RCT methodologyMcQuay and Moore, 199856: SRMixed conditions (low back, pancreatitis, osteoarthritis, dysmenorrhoea)TENS > control in 10/24 RCTsReviewers’ conclusion: evidence inconclusive – inadequate TENS dosesCarroll et al., 200157: SRMixed conditions (low back, pancreatitis, osteoarthritis, dysmenorshoea)TENS > control in 10/15 RCTsReviewers’ conclusion: evidence inconclusive – inadequate TENS doses

Gadsby and Flowerdew, 200062; Flowerdew and Gadsby, 199763: MALow back pain (6 RCTs)TENS > sham for pain relief (OR = 2.11)Reviewers’ conclusion: evidence of effect – poor RCT methodologyMilne et al., 200160; Brosseau et al., 200261: MALow back pain (5 RCTs, 421 patients)TENS = sham for pain relief (SMD = –0.207)Reviewers’ conclusion: evidence of no effect

belief that its effects are clinically meaningfuland/or a result of the electrical currents them-selves (Table 3).

TENS and postoperative pain Early reports suggested that TENS reduced post-operative pain and opioid consumption.43–45

However, a health technology assessment byReeve et al.46 reported that TENS was demon-strated to be of bene�t in only 12/20 randomizedcontrolled trials (RCTs). A systematic review byCarroll et al.42 reported that TENS did notproduce signi�cant bene�t when compared withplacebo in 15/17 RCTs. Both reviews used painrelief as the primary outcome measure, althoughpatients in some of the trials had access to addi-tional analgesic drugs so that those in sham andactive TENS groups could titrate analgesic con-sumption to achieve similar levels of pain relief.There were also minor inconsistencies in judge-ments of trial outcome between the reviewersbecause of the dif�culty of dichotomizing multi-ple outcome measures in RCTs. TENS is knownto be less effective for severe pains, like thoseassociated with thoracic surgical procedures, anddetecting reductions in mild pain (i.e., against asmall pre-TENS baseline) requires large samplesizes to achieve statistical power.47 Some RCTsused sample sizes with insuf�cient statisticalpower to detect potential differences betweengroups. Recently, my colleagues and I have per-

formed a meta-analysis of 21 RCTs that accountsfor some of these issues.48 We found that themean reduction in analgesic consumption afterTENS was 26.5% (range –6% to +51%) betterthan placebo. It is important that a subgroupanalysis of 11 trials (964 patients) that met ourcriteria for optimal TENS dosage (i.e., a strong,subnoxious electrical stimulation) reported amean weighted reduction in analgesic consump-tion of 35.5% (range 14–51%) better thanplacebo. In the trials without explicit con�rma-tion of optimal TENS dosage, the mean weightedanalgesic consumption was 4.1% (range –10% to+29%) in favour of active TENS. The differencein favour of adequate stimulation was highly sig-ni�cant (p = 0.0002). This suggests that adequateTENS technique is necessary in order to achievean effect.

TENS and labour painAugustinsson et al. pioneered the use of TENS inlabour pain by delivering currents to areas of thespinal cord that correspond to the input of noci-ceptive afferents associated with the �rst andsecond stages of labour (e.g., T10–L1 and S2–S4respectively).49 Early reports of TENS’ successresulted in the design of specialized obstetricTENS devices with dual channel output and‘boost’ controls for contraction pain. Despiteextensive use of TENS, systematic reviews con-clude that TENS provides little, if any, pain relief


Pain Reviews 2001; 8: 121–158

Price and Pandyan, 200158: MAPoststroke shoulder pain (4 RCTs, 170 patients); any surface ESES = sham/no treatment control for pain relief (WMD = 0.13)ES > sham/no treatment control for range of movement (WMD = 9.17)Reviewers’ conclusion: evidence inconclusive

Osiri et al., 200265: MAKnee osteoarthritis (7 RCTs, 294 patients)TENS > sham for pain relief (SMD = –0.448, although only 2/7 RCTs +ve)Reviewers’ conclusion: evidence of effect – pain relief

Proctor et al., 200264: MAPrimary dysmenorrhoea (8 RCTs, 213 patients)HF TENS > sham for pain relief (OR = 7.2)LF TENS = sham for pain relief (OR = 1.3)Reviewers’ conclusion: evidence of effect – pain relief for HF TENS only

SR: systematic review; RCT: randomized controlled trial; MWD: mean weighted difference; MA: meta-analysis;OR: odds ratio; SMD, standardized mean difference; ES, electrical stimulation; WMD, weighted mean differ-ence (= MWD); HF, high-frequency; LF, low-frequency

132 MI Johnson

Pain Reviews 2001; 8: 121–158

Table 4 Common characteristics of ‘generic categories’ TENS-like devices (taken in part from Table 3 in:Johnson MI. A critical review of the analgesic effects of TENS-like devices. Phys Ther Rev 2001; 6:153–7310)

Typical Standard TENS IFT MET HVPCcharacteristics

Delivery system 1 channel Quadripolar = 2 1 channel 1 channel(2 electrodes) channels (4 (2 electrodes) (2 electrodes)

electrodes) Single pointBipolar = 1 channel pen electrode(2 electrodes) Suction electrodes sometimes used

Pulse generator Hand-held Desktop and Desktop and Desktop andhand-held hand-held hand-held

Recommended Site of pain Site of pain Site of pain Site of painelectrode position Either side of Either side of

wound woundAcupuncture/ Motor point fortrigger points muscleTranscranial stimulation

Recommended Self-administration Under Under supervision Under treatment regimen as required supervision of therapist and supervision of

Continuous of therapist self-admistration therapist stimulation whenever Intermittent Intermittent stimulation Intemittent stimulation in pain stimulation (e.g., (e.g., ~20–60 min (e.g., ~20–60 min

~30 mins during for 1–3 times a day) for 1–3 times visit to clinic) a day)

Waveform Monophasic Amplitude- Modi�ed Twin peak Symmetrical biphasic modulated square direct monophasic Asymmetrical biphasic interference current with spiked pulse

wave generated monophasic orby 2 out-of-phase biphasic pulsesinusoidal currents changing polarity

at regular intervals

Amplitude + 1–60 mA 1–60 mA 1–600 µA 1–2 Aintensity Non-noxious Non-noxious No paraesthesia Paraesthesia

paraesthesia paraesthesia (i.e., below sensorydetection threshold)

Pulse rate Adjustable Adjustable Adjustable Adjustable1–250 pps 1–250 Hz for 1–5000 pps 1–120 pps

amplitude-modulatedwave Carrier wave2000–4000 Hz

Pulse duration Fixed and/or Carrier waves = Fixed and/or <100 µsadjustable unknown adjustable50–1000 µs Range unknown

Pulse pattern Continuous Amplitude- Continuous ContinuousBurst modulated BurstModulated frequency, wave can be Modulatedamplitude and pulse continuous or amplitudeduration modulated in

frequencyusing sweepsand swing patterns


Pain Reviews 2001; 8: 121–158

during labour.46,50,51 Carroll et al.50 reported that10/10 RCTs showed that pain relief scores pro-duced by TENS were no greater than shamTENS or a no treatment control. However, theself-report of pain relief may have been compro-mised by access to additional analgesics in someof the RCTs. The �nding that analgesic inter-vention may be less likely with TENS, asreported in the original systematic review,51 wasnot con�rmed in the updated review when datafrom an additional study was added.50

These �ndings seem to con�ict with clinicalexperience where midwives and patients reportsatisfaction with TENS’ effects.52 It is possiblethat pain relief ratings were in�uenced by �uctu-ating emotional and physical conditions duringlabour because one trial found that signi�cantlymore women and midwives favoured activerather than sham TENS when recorded underdouble-blind conditions at the end of childbirth.53

After childbirth, women are more likely to berelaxed and perhaps better able to re�ect on theeffects of the intervention. The systematicreviews also included RCTs that used unconven-tional TENS devices.54,55 These studies usedLimoge currents, which are administered tran-scranially and clearly differ from conventionalobstetric TENS (see section on TCES). It is inter-esting that both studies reported that Limogecurrents produced analgesic sparing effects whencompared with sham or no-treatment control.

TENS and chronic painA large number of clinical trials suggest thatTENS is useful for chronic pain. Three system-atic reviews have examined TENS’ effectivenesson mixed populations of chronic pain patients.Reeve et al. reported that TENS was more effec-tive than sham (n = 7) or no treatment (n = 2) in9/20 RCTs.46 McQuay and Moore stated thatTENS was better than sham TENS, placebo pills,or inappropriate electrode placements in 10/24RCTs.56 Carroll et al. reported that TENS pro-vided better pain relief than sham or no treat-ment in 10/15 RCTs. All reviewers concludedthat the evidence for TENS in chronic pain wasinconclusive.57

Reviews on speci�c populations of chronicpain patients are also inconclusive. A meta-analy-sis of any form of surface electrical stimulation

on 170 patients with poststroke shoulder painfound no signi�cant change in pain incidence(odds ratio = 0.64) or pain intensity (standardizedmean difference (SMD) = 0.13) after electricalstimulation compared with control.58,59 However,electrical stimulation improved the pain-freerange of passive humeral lateral rotation(weighted mean difference (WMD) = 9.17) andreduced the severity of glenohumeral subluxation(SMD = –1.13). For low back pain the �ndings ofreviews have been contradictory. A meta-analy-sis on 321 patients reported no statistically sig-ni�cant differences between active and shamTENS for pain relief.60,61 In contrast, a meta-analysis on 288 patients reported that TENSreduced pain and improved the range ofmotion.62,63 The overall odds ratio for pain reliefagainst placebo was only 2.11, although an oddsratio of 7.22 was reported in favour of AL-TENS.However, RCTs on AL-TENS did not state thatTENS generated muscle contractions, which isconsidered to be a prerequisite for AL-TENS. Ameta-analysis of the effect of TENS on pain asso-ciated with primary dysmenorrhoea reported thathigh-frequency but not low-frequency TENS wasmore effective for pain relief than sham.64 Ameta-analysis of 294 patients with kneeosteoarthritis reported that TENS produced sig-ni�cantly better pain relief and reductions inknee stiffness than placebo.65

All reviewers conclude that the low method-ological quality of TENS trials has contributed tothe uncertainty in the clinical evidence for effec-tive use in chronic pain. Underdosing of TENShas been recognized as a problem and some trialsmeasure outcome after a single TENS interven-tion or following a course of intermittent TENStreatments.57 This differs from clinical practice,where long-term users of TENS administer itover long periods of time because the effects ofTENS appear to be maximal when the device isswitched on.15 Nevertheless, the uncertaintyabout the clinical effectiveness of standard TENSdevices for pain relief has questioned it as aviable treatment option. Attempts to improveef�cacy by searching for optimal stimulator set-tings have largely been unsuccessful. As a result,health care professionals are turning to commer-cially available TENS-like devices with noveltechnical speci�cations that have emerged from

134 MI Johnson

Pain Reviews 2001; 8: 121–158

other areas of health care. At present, informa-tion about the effectiveness of TENS-like devicesis limited and decisions about device selection arebeing based on unreliable sources such as manu-facturers’ material or hearsay from colleagues.An assessment of the merits of some of the com-mercially available TENS-like devices is needed.

De� ning and categorizingTENS-like devicesFor the purpose of this review TENS-like devicesare de�ned as any stimulating device that deliv-ers electrical currents across the intact surface ofthe skin and whose generic name differs fromTENS. Potential TENS-like devices were identi-�ed from a cursory search of published literature,coupled with discussions with colleagues in the�eld. This was followed by searches ofMEDLINE (1966–2001) using device namesidenti�ed from the cursory search and the keywords ‘transcutaneous electrical nerve stimula-tion’ and ‘electrical stimulation therapy’. Allpotential links to related articles were followed,as were manual searches of items given in refer-ence lists. Information from manufacturers andthe Internet was used wherever possible to helpto determine technical speci�cations, recom-mended treatment procedures, and establishclaims of effectiveness.

The search identi�ed a variety of TENS-likedevices, although categorization according toformal criteria was impossible. Some devicescould be differentiated according to output char-acteristics (e.g., IFT, MET and HVPC; Table 4).Some devices could be differentiated accordingto the procedures used to deliver the currents(e.g., TENS-pens and TCES). Some could be dif-ferentiated according to novel principles ofaction (e.g., stimulators trying to overcomeTENS tolerance, TSE, APS and HWT; Table 5).There was much overlap between these divisions.For example, MET could be administered tran-scranially (e.g., as a type of TCES) or using aTENS-pen. Consequently, each TENS-likedevice is discussed separately for reasons of con-venience (Table 6).

Interferential currenttherapyIFT was developed in the 1950s and has remainedfor the most part within the discipline of physio-therapy.66 Surveys have shown that IFT is usedthroughout the world67,68 and there appeared tobe more published information on IFT than anyof the other TENS-like device in this review.Three textbooks on IFT were found thatdescribed the clinical use of the modality basedon the personal experience of the authors.69–71

There was an absence of good-quality experi-mental work to support the claims made in thetextbooks.67,72,73 IFT is most commonly used forpain relief74 although advocates claim that it willalso reduce in�ammation, assist tissue repair(including bone fractures) and re-educate muscle(especially for incontinence).69–71,75,76 IFT devicesare more expensive than standard TENS devicesand tend to reside in physiotherapy clinicsbecause they are relatively large. Recently, somebattery-operated hand-held IFT devices haveappeared on the market.

The purpose of IFT appears to be to delivercurrents to deep-seated structures. IFT stimula-tors are designed to generate an amplitude-mod-ulated interference wave, sometimes called theIFT ‘beat’. This wave is created by two out-of-phase currents that collide with each other togenerate an interference wave with a frequencyusually between 1 Hz and 200 Hz (Figure 7). Thetwo out-of-phase currents are delivered at fre-quencies between 2 Hz and 4 kHz because suchhigh-frequency short cycle duration waves willovercome skin impedance and penetrate deepbody structures.69–71,77–79 Advocates argue thatthese high-frequency kilohertz currents act asweak stimuli for nervous tissue, so a low fre-quency amplitude-modulated wave is created inorder to excite neurones.

Traditionally, the interference wave wascreated within the tissue by delivering two out-of-phase currents across the skin via four elec-trodes (termed quadripolar IFT), althoughnowadays the interference wave is often pre-modulated within the IFT device and deliveredvia two electrodes (bipolar IFT). IFT deviceshave an array of settings. The amplitude-modu-lated wave can be set at frequencies between 1Hz and 200 Hz and can �uctuate between upper

F

Pain Reviews 2001; 8: 121–158

and lower preset boundaries (termed the sweep)over a set time duration (termed the swingpattern). For example, a 6 L 6 swing patterndelivers amplitude-modulated frequencies that�uctuate between preset lower and upper fre-quencies over a 6-second time period. A 6 L 6swing pattern delivers amplitude-modulatedwaves at the lower frequency for 6 s and then atits upper frequency for 6 s.

When used for pain relief, IFT is delivered togenerate a strong but comfortable electricalparaesthesia at the site of the pain. This approachis comparable with conventional TENS and islikely to generate Ab activity and segmental anal-gesia. Similarities in administration proceduresfor IFT and conventional TENS have led somecommentators to challenge assumed differences

in analgesic pro�les between the two modali-ties.66,73,80 Studies using healthy people havefound that IFT elevates an experimentallyinduced cold pain threshold and reduces experi-mentally induced ischaemic pain when comparedwith sham, although there were no differences inIFT effects when compared with conventionalTENS.19,81,82 It is claimed that different ampli-tude-modulated wave frequencies selectivelyactivate different populations of nerve �bres togenerate speci�c physiological outcomes. Forexample, Savage70 claims that frequencies of100–130 Hz are in the analgesic range and thesedative range, and that frequencies of 5–100 Hzactivate autonomic nerves. No evidence could befound to support such claims. Furthermore, thephysiological rationale for including frequency

Figure 7

Time

Channel A4000Hz

Channel B4100Hz

AMF100Hz

Cu

rren

t A

mp

litu

de

Amplitude-Modulated Wave within deep seated tissue

B

BA

A

Figure 7 Principles used to generate an amplitude-modulated interference wave within deep tissue. Darkshaded electrodes attached anterior and lighter shaded electrodes attached posterior (A: electrodes forchannel A; B: electrodes for channel B) (adapted from Figure 1 in: Johnson MI, Tabasam G. A double blindplacebo controlled investigation into the analgesic effecs of interferential currents (IFC) and transcutaneouselectrical nerve stimulation (TENS) on cold induced pain in healthy subjects. Physiother Theory Pract 1999;15: 217–3319)


136 MI Johnson

Pain Reviews 2001; 8: 121–158

Tab

le 5

Com

mon

cha

ract

eris

tics

of s

ome

othe

r T

EN

S-li

ke d

evic

es (

take

n in

par

t fr

om T

able

3 i

n: J

ohns

on M

I. A

cri

tical

rev

iew

of

the

anal

gesi

c ef

fect

s of

TE

NS-li

ke d

evic

es.

Phys

The

r R

ev 2

001

; 6

: 1

53

–73

10)

Typ

ical

TE

NS

-pen

TC

ES

usi

ngS

timul

ator

s to

TS

EA

PS

HW

Tch

arac

teri

stic

s(P

ain®

Gon

e)L

imog

e cu

rren

tsre

duce

TE

NS

tole

ranc

e (C

odet

ron)

Del

iver

y sy

stem

Sin

gle

poin

t1

cha

nnel

(3

Cur

rent

s de

liver

ed1

cha

nnel

(2

1 c

hann

el (

21

cha

nnel

(2

p

en e

lect

rode

elec

trod

es)

rand

omly

to

1el

ectr

odes

)el

ectr

odes

)el

ectr

odes

)of

6 a

ctiv

eel

ectr

odes

Pul

se g

ener

ator

Han

d-he

ldD

eskt

op/h

and-

held

Des

ktop

Cod

etro

nH

and-

held

Des

ktop

AP

SD

eskt

op a

nd

pen

dev

ice

Lim

oge

devi

cede

vice

TS

E d

evic

ede

vice

hand

-hel

d us

ing

HW

T d

evic

esp

iezo

elec

tric

elem

ents

Rec

omm

ende

dS

ite o

f pa

in2

pos

itive

Acu

punc

ture

Spi

nal

cord

at

Site

of

pain

Site

of

pain

elec

trod

eA

cupu

nctu

reel

ectr

odes

in

poi

nts

T1

and

T1

2po

sitio

np

oint

sre

trom

asto

idor

C3

and

C5

regi

on a

nd 1

nega

tive

elec

trod

ebe

twee

ney

ebro

ws

Rec

omm

ende

d3

0–4

0In

term

itten

tIn

term

itten

tIn

term

itten

tIn

term

itten

tC

ontin

uous

tr

eatm

ent

indi

vidu

alst

imul

atio

nst

imul

atio

nst

imul

atio

nst

imul

atio

nst

imul

atio

n re

gim

ensh

ocks

Stim

ulat

ion

(e.g

. ~

30

min

(e.g

. ~

20

min

for

eith

er 8

or

whe

neve

r re

peat

edpe

riod

s ap

pear

3 t

imes

a d

ay)

at a

tim

e)1

6 m

inut

es a

tin

pai

nw

hen

ever

to b

e lo

nga

time

pai

n re

turn

s(e

.g.

star

t 6

0m

in b

efor

em

edic

atio

n an

dco

ntin

ueth

roug

hout

the

time

of t

heph

arm

acol

ogic

alac

tion

of t

hedr

ug)


Pain Reviews 2001; 8: 121–158

Wav

efor

mS

ingl

eP

ositi

ve p

ulse

Squ

are

wav

eD

iffer

entia

ted/

Mon

opha

sic

Bip

hasi

c w

ave

Mon

opha

sic

(hig

h in

tens

ityw

ith D

Cre

ctan

gula

rsq

uare

pul

sew

ith

spik

ed p

ulse

shor

t du

ratio

n)cu

rren

t of

with

expo

nent

ial

follo

wed

by

opp

osite

expo

nent

ial

deca

yne

gativ

e pu

lse

pol

arity

deca

y an

d D

C(lo

w i

nten

sity

follo

win

gof

fset

of

5V

long

dur

atio

n)ea

ch p

ulse

deliv

ered

in

trai

ns (

burs

ts)

Am

plitu

de +

Low

am

pere

~

2m

A/3

0V

Mill

iam

pere

Low

am

pere

Mic

roam

pere

Mill

iam

pere

in

tens

ityhi

gh v

olta

ge<

60

m A

high

vol

tage

No

<1

0m

A l

ow

(e.g

. 6

µA/

Non

-nox

ious

N

opa

raes

thes

iaou

tput

to

15

,00

0V

)p

arae

sthe

sia

para

esth

esia

(i.e.

bel

ow‘r

educ

e N

on-n

oxio

usto

pin

pri

ck(i.

e. b

elow

sens

ory

heat

ing’

to

mild

pai

nse

nsor

yde

tect

ion

Non

-nox

ious

no

xiou

s pi

npri

ckde

tect

ion

thre

shol

d)p

arae

sthe

sia

sens

atio

nth

resh

old)

Pul

se r

ate

Ad

hoc

:1

25

kHz

Pre

sets

Pre

sets

Fixe

d at

Adj

usta

ble

or

dep

ends

on

inte

rrup

ted

incl

ude

incl

ude

~1

50

pps

pres

ets

rate

of

butt

onw

ith a

n1

, 2

, 4

, 2

00

pps

60

0–

betw

een

2 a

ndp

ress

inte

rmitt

ent

10

,00

0pp

s6

0pp

scu

rren

t of

83

Hz

Pul

se d

urat

ion

Unk

now

n bu

tP

ositi

ve p

hase

Fixe

d pr

eset

Fixe

d p

rese

tFi

xed

pres

etFi

xed

pres

et a

tat

�xe

d p

rese

tof

pul

sebe

twee

nbe

twee

n 1

.5be

twee

n 8

00

16

00

0µs

1

.7µs

,1

00

0–5

00

0µs

and

4µs

and

66

00

µsne

gativ

eph

ase

ofpu

lse

6.3

µs

Pul

se p

atte

rnA

d h

oc:

Tra

ins

of h

igh-

Con

tinuo

usC

ontin

uous

Con

tinuo

usC

ontin

uous

de

pen

ds o

nfr

eque

ncy

Bur

stp

atte

rn o

fpu

lses

butt

on p

ress

inte

rrup

ted

bylo

w f

requ

ency

puls

es

138 MI Johnson

Pain Reviews 2001; 8: 121–158

Tabl

e 6

TEN

S-lik

e de

vice

ide

ntity

. R

ando

miz

ed c

ontr

olle

d cl

inic

al t

rials

that

com

pare

the

ana

lges

ic e

ffect

s of

TEN

S-lik

e de

vice

s w

ith a

sta

ndar

d T

ENS

are

need

ed f

or a

ll ca

tego

ries

(take

n in

par

t fr

om T

able

4 in

: Jo

hnso

n M

I. A

crit

ical

rev

iew

of

the

anal

gesi

c ef

fect

s of

TEN

S-lik

e de

vice

s. P

hys

The

r R

ev20

01;

6 : 1

53–7

310)

Stan

dard

IFT

MET

HVPC

TEN

S-pe

nTCES

Stim

ulat

ors

toTS

EA

PSH

WT

TEN

Sus

ing

Lim

oge

redu

ce T

ENS

curr

ents

tole

ranc

e(C

odet

ron)

Mai

nPa

in r

elie

fPa

in r

elie

fAss

ist

Mus

cle

Pain

relie

fRed

uce

Pain

relie

fPa

in r

elie

fPa

in r

elie

fPa

in r

elie

fin

dica

tions

Mus

cle

tissu

estim

ulat

ion

anal

gesic

/stim

ulat

ion

heal

ing

Ass

ist

anae

sthe

ticAnt

i-Pa

in r

elie

ftis

sue

inta

kein

�am

mat

ory

healin

gPa

in r

elie

f

Cla

ims

for

Cur

rent

sCur

rent

sCur

rent

sCur

rent

sC

urre

nts

Cur

rent

sC

urre

nts

Cur

rent

sC

urre

nts

Cur

rent

s un

ique

ness

sele

ctively

excite

dee

p-m

imic

pass

eas

ilyac

tivat

edi

rect

lyre

duce

by-p

ass

skin

mim

icm

ore

activ

ate

seat

ed‘c

urre

nt o

fth

roug

hbo

dy’s p

ain

in�u

ence

nerv

ous

and

actio

nco

mfo

rtabl

e di

ffere

nttis

sue

inju

ry’ to

skin

to

relie

fbr

ain

system

dire

ctly

pote

ntia

lsth

an T

ENS

nerv

eac

cele

rate

activ

ate

system

func

tion

habi

tuat

ion

excite

Rel

atio

nshi

p �b

res

tohe

alin

gm

otor

and

mim

icce

ntra

lto

H-re�

ex

initi

ate

nerv

esel

ectro-

nerv

ous

unclea

rpa

inse

lect

ivel

yac

upun

ctur

esy

stem

mod

ulat

ory

tissu

e to

mec

hani

sms

redu

cece

ntra

lse

nsiti

zatio

n

Prin

cipl

e of

Prov

enU

ncle

arU

ncle

arU

ncle

arU

nclear

Unc

lear

Evid

ence

Inte

restin

gU

ncle

arU

ncle

ar

actio

n fo

rSi

mila

r to

may

be

due

Sim

ilar

toC

ould

be

Evid

ence

supp

orts

but

Sim

ilar

toSi

mila

r to

pain

relie

fstan

dard

to tiss

ue

stan

dard

no

ninv

asive

sugg

ests

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Pain Reviews 2001; 8: 121–158

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140 MI Johnson

Pain Reviews 2001; 8: 121–158

chophysiological outcomes when IFT was admin-istered in both the presence and the absence ofthe amplitude-modulated wave. Thus, it is possi-ble that any pain relieving effects of IFT are dueto the higher frequency current (i.e., 2–4 kHz)rather than to the amplitude-modulated wave.

Microcurrent electricaltherapyMET uses currents that are 1/1000th of anampere smaller than those delivered by standardTENS devices (milliamperes). Advocates claimthat MET devices can be used to accelerate tissuehealing and relieve pain, especially pain relatedto sporting injuries91–94 MET comes under arange of guises, including microcurrent electricalnerve stimulation, microamperage stimulation,low-intensity direct current, and pulsed low-intensity direct current. De�nitions of MET arevaried, although the American Physical TherapyAssociation has de�ned it as a low-intensitydirect current that delivers monophasic or bipha-sic pulsed microamperage currents across theintact surface of the skin.8 Often, MET devicesutilize adjustable pulse frequencies between 0.5pps and 150 pps with periodic reversals in polar-ity. MET can be delivered using probe electrodes(sometimes in the form of a pen) or pad elec-trodes, which are applied to acupuncture points,trigger points or over the site of pain. Some METdevices have a point �nder to detect areas of theskin with low resistance, which are believed tocorrespond to acupuncture points.95 MET canalso be administered on ear lobes and transcra-nially, where it is claimed that it will relievemigraine, headache, insomnia and stress.96

MET developed from the claim that tissuehealth is maintained by a direct current electricalsystem in the human body and that a shift in this‘normal current �ow’ occurs when tissue isdamaged97–99 This direct current shift wasdescribed as the ‘current of injury’, with a mag-nitude in the microampere range. Advocatesclaim that MET simulates this current of injuryto assist tissue growth and healing, and that mil-liampere currents delivered by standard TENSdevices are detrimental to this process ofrepair.100,101 They also claim that MET providespain relief, although it is unclear whether this is

sweeps and swing patterns in IFT device designis obscure. Systematic investigations into theeffects of different frequencies and swing pat-terns of IFT on experimentally induced pain inhealthy people has found that analgesia was notaffected by frequency or swing pattern when IFTwas administered at a strong but comfortableintensity without concurrent muscle contrac-tion.83–85

The majority of clinical reports on IFT effectsare anecdotal and lack appropriate controls.Taylor et al. reported no signi�cant differencesbetween the effects of sham and active IFT onpain and dysfunction in 40 patients suffering fromjaw pain.86 Quirk et al. found no additional ben-e�ts from IFT when compared with exercise in38 patients suffering pain and dysfunction asso-ciated osteoarthrosis of the knee.87 An RCT on152 patients by Werners et al.88 reported thatthere were no signi�cant differences in the mag-nitude of pain relief achieved using IFT whencompared with motorized lumbar traction withmassage management for low back pain. The lackof IFT effects in these controlled studies may bedue to underdosing of IFT because it is believedthat patients experience fatigue if stimulationlasts more than 30–40 min. Observations ofpatients using TENS at strong but comfortableintensities in a similar manner to that describedfor IFT suggest that this is not the case. Theacceptance of short duration IFT treatment maybe due to constraints of the clinical rota becausemost IFT treatment sessions take place in theclinical setting under the supervision of a thera-pist. Furthermore, applying IFT at the site of painmay not be the most appropriate approach;Hurley et al.89 have shown that IFT deliveredover the spinal nerve produced greater reduc-tions in functional disability when compared withIFT administered directly over the painful area.

Explanations of how IFT produces pain reliefare at best vague and tend to focus on ‘pain gates’and ‘endorphins’. The justi�cation for using anamplitude-modulated interference wave to stim-ulate neural tissue rather than a biphasic pulsedcurrent as generated by standard TENS devicesseems to be entirely speculative. Demmink11 hasreported that IFT modulation patterns could bereproduced in water but not in biological tissue,where current distribution was unpredictable.Palmer et al.90 found no differences in psy-


Pain Reviews 2001; 8: 121–158

a primary effect through direct action on theantinociceptive system or a secondary effect fromtissue healing. Users do not perceive MET cur-rents, so it seem likely that the putative mecha-nism of action differs from conventional TENS.A relatively large body of published research wasfound for MET that could be divided into effectson pain and on tissue healing.

MET and pain reliefInvestigations into the effects of MET on exper-imentally induced pain in healthy prople haveproduced contradictory results. Weber et al.reported no signi�cant differences betweenmassage, upper body ergometry, MET and a notreatment control on delayed-onset muscle sore-ness induced by high-intensity exercise in 40healthy volunteers.102 In contrast, Lambert et al.reported that MET reduced the severity ofdelayed-onset muscle soreness in 30 healthy menunder double-blind, placebo-controlled condi-tions.103 A study using cold-induced pain foundno signi�cant differences between active andplacebo MET on experimentally-induced painthreshold and pain intensity rating in 36 healthyvolunteers using single-blind methodology.104

evidence available from clinical trials is alsoinconclusive. Clinical trials on MET often lackmethodological rigor. For example, a report of adouble-blind placebo-controlled trial claimedthat MET signi�cantly reduced chronic back painin 40 patients, yet details about the statisticalanalysis were omitted from the report.105 METwas administered for two 6-second periods to 16points on the back, three times per week for twoweeks. No physiological rationale was given forsuch a prescriptive treatment regimen. Similarly,MET was given to the affected hands of 36patients with carpal tunnel syndrome for threetreatments per week for four to �ve weeks incombination with low-level laser acupunctureand other alternative therapies.106 Although itwas claimed that this treatment approach wassuccessful in relieving pain, it was not possible todetermine the exact contribution of MET.Clinical trials have also found that MET effectsare comparable to TENS in patients withmigraine and chronic headaches,107but less effec-tive than a laser for improving mobility and painin patients with degenerative joint disease.108

MET and tissue healingIt is possible that putative pain relief may be a by-product of the accelerated healing process. Initialreports of experiments in vitro suggested thatMET accelerates the healing of damaged tis-sue,109–112 possibly through increased protein syn-thesis100,101,113 or through antimicrobaleffects.114–116 However, two well-controlled animalstudies found that MET did not accelerate thehealing of experimentally induced wounds in ratsand Yucatan mini pigs.117,118 The editor of onejournal concluded that ‘the time has come to weighthe evidence and to face the accumulation of datafrom these and other reports indicating that thismodality [MET] does not assist in wound healingwhen used in the manner described’.119

Clinical evidence is also inconclusive.Encouraging reports of MET accelerating thehealing of ulcers and wounds are often under-mined by the lack of appropriate controlgroups.109,120–122 Carley and Wainapel123 adminis-tered MET for two hours twice a day for sixweeks and found that it accelerated the healingof ulcers in 30 patients when compared with con-ventional wound dressings. However, the absenceof a placebo control group meant that observedeffects may have been due to the act of givingMET rather than the electrical currents gener-ated by MET. Randomized double-blind sham-controlled multicentre studies on the effects ofelectrical stimulation on ulcers and wounds doexist, although it is not certain whether the typesof electrical stimulation used were strictly MET.Mulder124 found that pulsed electrical stimulationdecreased wound size by 56% when comparedwith a 33% reduction with sham on 59 patientswith open wounds of pressure, vascular and sur-gical origin. A similar study on 47 patients withchronic dermal ulcers found differences in woundsize and healing rate in favour of electrical stim-ulation.125 Pulsed cathodal electrical stimulationwas delivered twice daily at a pulse frequency of128 pps, although the peak amplitude of 29.2 mAwas higher than that seen for MET. A meta-analysis of 15 trials on a variety of forms of elec-trical stimulation reported that the healing ratewas 22% per week compared with 9% for con-trols.126 Unfortunately, �ndings on the relativeeffectiveness of the different types of electricalstimulation devices used in the studies wereinconclusive.

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Pain Reviews 2001; 8: 121–158

Rebox devices also deliver microampere cur-rents and, as a consequence, could be classed asMET. They were developed in the 1970s and usecurrent trains of unipolar rectangular pulses viaa charged probe electrode using microampereamplitudes (1–300 µA), pulse frequenciesbetween 200 Hz and 5000 Hz, and a pulse dura-tion of 50–250 µs.127,128 Available evidence aboutthe pain relieving effects of Rebox is con�icting.Johannsen et al.129 reported that Rebox improvedboth pain and function in patients with chroniclateral epicondylitis. In contrast, Hatten et al.reported that Rebox did not provide signi�cantpain relief in patients130 A placebo-controlledtrial by Nussbaum and Gabison showed no dif-ferences between active and placebo with dailytreatments of Rebox on experimentally-induceddelayed onset muscle soreness in 30 healthy vol-unteers.131

High-voltage pulsed currents HVPC, also known as high-voltage galvanic stim-ulation and high-voltage pulsed galvanic stimula-tion, have been used for muscle strengthening,wound healing and pain relief since the1940s.99,127, 128,132 Until recently HVPC deviceswere relatively large and resided in physiother-apy clinics, although, with advances in electronictechnology, modern HVPC devices can be similarin size to standard TENS devices and, as a con-sequence, are being marketed for pain andwound management. HVPC devices deliverdirect current with twin monophasic spikedpulses of 10–500 V (500 ohm load) with a shortpulse duration (microseconds) to increase pene-tration of tissue, leading to greater selectivity inrecruiting motor nerves in innervated muscle andimproved comfort for the patient. Pulses aredelivered at double pulse frequencies of between1 and 120 per second via a variety of types ofelectrodes including sponge, traditional carbonrubber and hand-held point electrodes.127,132

Much of the experimental work on HVPC hasfocused on claims that it assists wound healingand is out of the scope of this discussion.99,128 TwoRCTs of note have reported that HVPC assiststhe rate of healing of ulcers. Kloth and Feedar133

delivered HVPC to patients with decubitis ulcers

and reported that the healing rate was fasterwhen compared with sham. Grif�n et al.134

reported that HVPC signi�cantly increase thehealing rate of pressure ulcers in the pelvic regionwhen given at 100 pps and an intensity of 200 Vfor 1 h a day for 20 consecutive days.

Little experimental work on the effects ofHVPC on pain relief was found. A comparisonof the analgesic effects of HVPC with differenttypes of TENS on electrically induced painthreshold and tolerance in 14 healthy peoplefound no signi�cant differences between thegroups.135 Morris and Newton136 investigated theeffects of HVPC on 28 patients with symptomsof pain and discomfort in the perirectal or rectalregion (levator ani syndrome). HVPC wereadministered using a rectal probe for 1 h at a fre-quency of 120 Hz and at the maximum intensitythat the patients could tolerate. They reportedthat 50% of these patients had pain or symptomrelief after an average of eight treatments,although the study lacked a control group.Clearly, more experimental work is needed.

TENS-pensA variety of hand-held pain relieving ‘pens’ areavailable on the market, which deliver electricalcurrents to the intact surface of the skin using asingle point electrode. TENS-pens are availableas stand-alone battery operated devices orattached to battery operated pulse generators viaa lead. The single point electrode used in TENS-pens encourages users to deliver currents to dis-crete points on the surface of the body.Acupuncture points are often used as sites forstimulation and some devices incorporate anacupuncture point �nder that detects low resis-tance on the skin. However, advertizing materialrecommends that TENS-pens can also be used tostimulate trigger points or the site of pain. Theuser needs to hold the pen during stimulation, sotreatment times tend to be short and often lessthan a minute. It is therefore assumed that pain-relieving effects occur predominantly post-stimulation.

The technical speci�cations of TENS-pens varyconsiderably between manufacturers, with avail-able pens delivering currents in both milliampere(i.e., using a standard TENS pulse generator) and


Pain Reviews 2001; 8: 121–158

microampere (i.e., using a standard MET gener-ator) ranges. Milliampere pens that deliverpulsed currents at strong but nonnoxious intensi-ties are likely to activate large diameter nerve�bres and mimic the actions of conventionalTENS. It is not known whether there are differ-ences in outcome when conventional TENS cur-rents are delivered to acupuncture points ratherthan to the site of pain because experimental evi-dence is lacking. A review of studies that assessedthe pain relieving effects of TENS when deliv-ered to acupuncture points using traditional elec-trode pads reported con�icting results.33

Furthermore, it is not known whether deliveringnonnoxious pulsed currents via a pen producesdifferent outcomes to those obtained by usingself-adhesive surface electrodes. Nevertheless, asthe poststimulation effects of nonnoxious pulsedcurrents (i.e., conventional TENS) are shortlived, the delivery of currents intermittently via aTENS-pen would be of limited bene�t. METdevices sometimes use pen electrodes to admin-ister microampere currents. Whether this pro-duces different treatment outcomes to those seenwhen MET is administered using pad electrodesis not known.

Recently, high-voltage single-pulse TENS-pens(e.g., Pain®Gone) have appeared on the UKmarket for treatment of minor ailments andpainful conditions such as arthritis, back pain,headache and sports injuries.137 High-voltageTENS-pens generate a single pulse when twocrystals (piezoelectric elements) are forcedtogether by a plunger. Each pulse has a highvoltage (claimed to be 15,000 V) and short pulseduration, resulting in a 6 µA ‘shock’. Advocatesclaim that the high-voltage TENS-pens delivercurrents in the microampere range, yet theiroutput characteristics clearly differ from METand are probably more akin to HVPC.

High-voltage TENS-pens are claimed to gen-erate low-frequency stimulation (1–2 pps),although the frequency of pulse delivery will bedependent on the rate of button pressing by theuser, and is more likely to be ad hoc and asyn-chronous. Manufacturers recommend thatpatients should click the stimulating button 30–40times over acupuncture points or over the site ofpain as this will result in effects that are similarto TENS and acupuncture. Descriptions of this

mechanism of action are super�cial and incom-plete. The ‘shock’ produces a sensation thatresembles a pinprick and can be mildly painful,depending on the body site stimulated. This sug-gests that cutaneous Ad �bres are active. Adafferents are believed to have a role in acupunc-ture analgesia and are known to trigger diffusenoxious inhibitory controls and releaseendorphins. Thus, high-voltage TENS-pens mayinitiate acupuncture-like mechanisms (onacupuncture points) or counterirritation (onremote body sites) or both. It is not knownwhether the effects of high-voltage TENS-pensare dependent on the site of application.

Information on the clinical effectiveness ofhigh-voltage TENS-pens is lacking. One unpub-lished manuscript of an open uncontrolled clini-cal trial on 25 patients was identi�ed.137 Eachpatient received 25 clicks of the high-voltageTENS-pen once a day for three to �ve days,either over or just above the most painful area.Good to excellent pain relief that occurred imme-diately after treatment and lasted for ‘somehours’ was reported by 76% of patients. Similarresults were obtained in an uncontrolled trial on36 patients with chronic musculoskeletal pain.138

There was no placebo control group in eitherstudy, so it is possible that the pain relievingeffects were produced by the act of giving thetreatment rather than the electrical currents.Clearly, randomized controlled clinical trials areneeded.

Transcutaneous cranial electrical stimulationTCES has been used for over 30 years in reha-bilitation medicine in the USA for insomnia,anxiety, depression, drug withdrawal, pain relief,and to reduce consumption of analgesics andanaesthetics.139,140 Other names for TCES includecranial electrotherapy stimulation, transcranialelectrotherapy, neuroelectric therapy, transcra-nial electrostimulation, and electrosleep.Electrode positions for TCES give the techniqueits identity and include: (1) attaching an electrodeto each earlobe; or (2) attaching electrodes toeach temple; or (3) attaching two positive elec-trodes in the retromastoid region and a negativeelectrode between the eyebrows (Limoge cur-

144 MI Johnson

Pain Reviews 2001; 8: 121–158

rents). TCES treatment usually lasts for 30–60minutes and is repeated once or twice daily. Ituses MET-like currents with current amplitudesbelow 1 mA. Pulse repetition rates of 100 pps arepopular, although they can range from 0.5 pps to15,000 pps, depending on the device.

There does not seem to be a general consen-sus about the speci�c mechanism by which TCEScould alleviate pain. Advocates claim that theoutput characteristics of TCES devices enablecurrents to reach the brain directly from the siteof stimulation and that the currents affect brain function through direct action on neuronalactivity and/or endogenous pharmacology.Animal and human studies have implicatedendorphins, serotonin, cortisol and many otheragents as potential mediators of TCESeffects.140–143 Experimental work suggests thatTCES may potentiate the effects of opiates, neuroleptics and anxiolytics, allowing reductionsin drug medication during anaesthetic proce-dures.144–153

The �ndings of clinical trials on TCES areencouraging. A multicentre double-blind RCT on100 patients with tension headache reported thatTCES signi�cantly reduced pain intensity whencompared with placebo.154 RCTs have also foundpositive effects of TCES on stress-related symp-toms in people with closed head injury155 and inreducing anxiety during routine dental proce-dures,156 which may indirectly reduce pain.Recently, Scherder et al.157 reported that TCESproduced no improvements in cognition and(affective) behaviour in 18 patients withAlzheimer’s disease when compared withplacebo. One meta-analysis on the clinical effec-tiveness of TCES versus sham was found.158

Eighteen RCTS were identi�ed, out of which 14had suf�cient data to pool. TCES was signi�-cantly more effective than sham treatment foranxiety (eight trials) and headache (two trials),but not signi�cant for brain dysfunction (twotrials) and insomnia (two trials).

TCES using Limoge currents has attractedattention for use in anaesthesic proceduresbecause it has been claimed to reduce con-sumption of analgesics and anaesthet-ics.140,144,145,148,149,153 One group claims to haveadministered TCES using Limoge currents inover 30,000 major interventions and also to aid

drug withdrawal in 4000 opioid addicted patients,without any adverse events.140. Limoge currentsare high-frequency pulses (166 kHz; on-time = 1ms) interrupted with a repetitive low-frequencypulse (83 Hz; on-time = 4 ms) and delivered atlow intensities of approximately 2 mA.159 Eachpulse has a high-amplitude, short duration (1.7µs) positive phase and this is followed by a low-amplitude, long duration negative phase (6.3 µs).These pulses are delivered in trains (bursts).Some Limoge devices deliver currents at 167kHz, interrupted with an intermittent current of77 Hz, 83 Hz or 100 Hz. Two studies included insystematic reviews on TENS and labour painfound that Limoge currents reduced additionalanalgesic intervention in women experiencinglabour pain when compared with a shamdevice.54,55

Stimulators to overcometolerance to TENSReports have suggested that some patientsbecome tolerant to the pain-relieving effects ofcurrents delivered by a standard TENS device,which may result from nervous system habitua-tion to repetitive monotonous stimuli.160–162 In anattempt to overcome nervous system habituationand the resultant TENS tolerance, some devicesnow have output characteristics that �uctuatebetween preset limits during stimulation.

One common approach to TENS tolerance hasbeen to �uctuate pulse frequency (i.e., frequencymodulation) between upper and lower bound-aries in a similar manner to that described forIFT. Frequency modulation on TENS devices hasproved popular with patients and has been shownto be effective in relieving pain.163–165 However,it is not known whether frequency modulationproduces clinically meaningful reductions in theincidence of TENS tolerance. Another approachhas been to deliver pulses randomly (i.e., randomfrequency). Random frequency TENS has beenshown to elevate the experimental pain thresholdin healthy people when compared with placebo,but the magnitude of the change was no differ-ent to that seen with other modes of TENS.14 Noclinical studies were found that had assessed theeffects of random frequency TENS on TENStolerance.


Pain Reviews 2001; 8: 121–158

An alternative approach to overcome nervoussystem habituation has been to deliver TENSpulses randomly to different body sites. Codetronis a TENS-like device that delivers low-frequency(2–4 pps) square waves with a pulse duration of1 ms in a random order to one of six active elec-trode pads, which are usually positioned onacupuncture points. A small direct current ofopposite polarity follows each pulse in order toavoid polarization of tissue. Codetron has beenshown to increase the amplitude of corticalevoked potentials, indicative of a reduction innervous system habituation, in healthy volunteerswhen compared with pulses delivered using con-ventional TENS.166 Manufacturers also claim thatCodetron mimics the effects of electroacupunc-ture and AL-TENS. Patients are advised toadminister Codetron currents at the highestintensity that they can tolerate, providing they donot produce frank pain.167–169 It is plausible,therefore, that Codetron generates activity insmall diameter nerve �bres, resulting in extraseg-mental analgesia, in a manner similar to elec-troacupuncture.

Clinical trials of Codetron have produced con-�icting results. It has been shown to provide over30% pain relief in 107 of 137 patients with avariety of painful conditions.168 A double-blindrandomized sham controlled trial in 37 patientswith osteoarthritis of the knee found thatCodetron signi�cantly improved pain when com-pared with sham (low-intensity TENS).69 It hasalso been reported that Codetron reduces mus-culoskeletal pain to the same extent as elec-troacupuncture when delivered to acupuncturepoints at 4 pps and 200 pps at intensities justbelow pain.170 Patients were given 20-minutetreatment sessions, once or twice a week for amaximum of 12 treatments, depending on need.Telephone interviews four to eight months afterthe end of the study showed that patients in theCodetron group reported greater improvementwhen compared with those in the elec-troacupuncture group. In contrast, a RCT thatexamined the effect of adding Codetron to anexercise programme in 58 low back pain patientsfound no differences between actual or placebo(no current) stimulation for disability or painscores.166 Patients did improve with exercise.

Transcutaneous spinal electroanalgesia TSE, which has attracted much attention in theUK since its introduction in 1995, is indicated forminor aches and pains, migraine and stress.171

Preliminary data suggest that TSE may help toreduce general practitioner consultation ratesand that patients are satis�ed with its effects.172,173

TSE delivers pulsed currents with a high fre-quency (600–10,00 pps), high voltage and shortpulse duration (1.5–4 µs) via two pad electrodespositioned either at T1 and T12 or straddlingC3–C5. The intention of TSE is to activateexcitable tissue in the spinal cord in order toreduce central sensitization by ‘resetting’ centralnervous system neuronal activity back to its pre-sensitized state.171 Physiological studies suggestthat conventional TENS may reduce central sen-sitization,174–177 although there have so far beenno experiments investigating the effects of TSE.If proved, TSE could be useful in the manage-ment of hyperalgesia and allodynia.

The output characteristics of TSE devices aredesigned to overcome skin resistance so that cur-rents bypass the skin and directly affect spinalcord circuitry. Patients do not usually experienceelectrical paraesthesia during TSE, so it is likelythat cutaneous nerves are not activated to anyappreciable extent and therefore the mechanismof action is different from conventional TENSmechanisms (i.e., activation of Ab afferents). Itis also claimed that, because peripheral nerveinput converges at the spinal cord, TSE effectswill be widespread over the body.171

Studies on the effects of TSE are sparse. Theinitial promise of TSE was based on observationsthat it reduced pain by 60% in over two-thirds ofa sample of 100 pain patients.171 A preliminaryRCT on eight patients suffering musculoskeletalpain found that TSE produced signi�cantlygreater reductions in pain measures than TENS.Each patient received one 20-minute treatmentof TSE (10 kHz, 1.5 µs) and one 20-minute treat-ment of TENS (100 pps, 200 µs) in a randomized,double-blind crossover fashion. Both TSE andTENS were applied over T1 and T12. Theauthors recognized that this was not the normalway of administering TENS and that the studylacked power owing to the small sample size.

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Pain Reviews 2001; 8: 121–158

However, these initial �ndings suggested that theoutput characteristics of TSE produced morepain relief than those from a standard TENSdevice when administered at spinal sites.

Subsequent reports have been less encourag-ing. Towell et al.178conducted a study using 60healthy people to investigate the effects of TSEon mood and mechanical pain tolerance. Whenapplied to the spinal cord for 30 minutes, itreduced tolerance to mechanical pain when com-pared with sham TSE, suggesting that TSE hadmade the experimental pain worse. However,TSE was found signi�cantly to elevate mood. Asecond experiment by the same group appliedTSE to the shoulder joint and found no differ-ences in mood or pain tolerance to experimentalpain in healthy people when compared withsham. Studies reported in conference proceed-ings con�rm the lack of analgesic effect.Hilberstadt et al.179 reported that TSE did notalter pain when administered in 10-day periodsto two patients with low back pain. A series ofdouble-blind placebo controlled trials conductedby Heffernan and Rowbotham180 found that TSEdid not reduce pain or the need for additionalanalgesic interventions when compared withsham TSE in acute and chronic pain settings. Atleast one other RCT on the effects of TSE forpain after breast cancer treatment was found,although the current status of this trial isunknown.181

Action potential simulation It is claimed that APS provides pain relief,reduces in�ammation and swelling, enhanceslocal blood circulation, increases mobility, regen-erates cell and bone growth, and generatesadenosine triphosphate (ATP).182–184. The term‘action potential simulation’ derives from claimsthat APS devices generate electrical currents thatare similar in shape to nerve action poten-tials.101,184 It is unclear whether APS currents aredesigned to trigger action potentials or whetherthey simulate changes in membrane potentialsresulting from neural activity.

APS delivers monophasic square waves withexponential decay and a DC offset that remainsat 5 V. APS uses a long pulse duration between800 µs and 6.6 ms, a pulse frequency �xed at ~150

pps and a pulse amplitude between 0 and 24.4mA into a 500 ohm load. It is claimed that APSis a unique type of MET, although most articleson APS do not make this explicit.101,113 In someexperiments APS was delivered using low-current amplitudes (e.g., between 0.70 mA and1.7 mA) with patients being unable to perceivecurrents.182,185 However, it has also been deliv-ered at doses that appear to be ‘strong’ and pro-ducing electrical paraesthesia.182,186 APS isadministered using two electrodes attached closeto the site of pain and protocols used in somepublished trials seem to focus on treatment timesin multiples of 8 min (e.g., 8 and 16 min) althoughthe rationale for this approach is vague.182,183

Descriptions of the hypothetical mechanism ofaction of APS are ambiguous, and general state-ments that APS leads to excitation of the centralnervous system and the release of neurohor-mones are common.184,187 It is claimed that theDC offset in the APS waveform increases pro-duction of ATP and also creates tissue polariza-tion, resulting in increased levels of oxygen andcatabolism and leading to the removal of wastesubstances of tissue damage.101,113,184 It is inter-esting that tissue polarization is seen as anadverse effect for Codetron but is considered tobe of bene�t for APS.

The majority of experimental work on theeffects of APS originates in South Africa, wherethe device was originally designed. A double-blind placebo controlled study found that APSincreased plasma levels of L-enkephalin andmelatonin and reduced Beta-endorphin whencompared with sham APS (no current) inpatients suffering chronic low back pain.187 Nochanges in plasma serotonin or cortisol levelswere found and the authors speculated thatdecreasing plasma beta-endorphin would help toreduce in�ammation, although this could not beproved within their experiment because they didnot record changes in in�ammation directly.Experimental evidence on the effect of TENS onplasma opioids is con�icting.188–190 An open trialusing 285 patients with a variety of chronic painconditions found that APS improved pain andmobility, although the study lacked a controlgroup.183

Odendaal and Joubert185 examined the effectsof APS in a placebo controlled trial on 76


Pain Reviews 2001; 8: 121–158

patients with chronic low back pain and claimedthat APS ‘may be an effective treatment’. Thedata suggested that there were no differencesbetween APS and sham APS groups, althoughthe authors argued that the trial population wastoo small to conduct a between-group analysis.Berger and Matzner182 examined the effects ofAPS, TENS and placebo on mobility and swellingin 99 patients suffering from osteoarthritis,reporting that APS, TENS and placebo improvedpain. However, no effects were found betweentreatment groups, suggesting that the act ofgiving APS, rather than the electrical currentsdelivered by APS, produced the reduction inpain. The authors argued that APS was a viabletreatment option because it was unacceptable toadminister placebos in clinical practice. A moreappropriate interpretation of these �ndingswould be that APS, TENS and placebo areequally ineffective in the treatment of patientswith osteoarthritis. Double-blind studies on theeffects of APS, TENS and IFT on skin tempera-ture and mechanical pain threshold in healthypeople have also failed to �nd any signi�cant dif-ferences between groups.85,191

H-wave therapy Manufacturers claim that HWT is useful in thetreatment of soft tissue injuries by promotinghealing, reducing in�ammation and oedema, andrelieving pain. It has been used to treat neuro-pathic pain associated with diabetes192 and fordental anaesthesia.193 It seems that HWT wasdeveloped to reproduce the H-re�ex (Hoffmanre�ex), hence the name, although a suitableexplanation of the relationship between theHoffman re�ex, HWT and analgesia could not befound. Manufacturers state that HWT currentspass through the skin without causing discomfortand that the output characteristics mimic thosefound in the body, although how this relates tophysiological mechanisms is not clear.

HWT is administered by using two electrodesat the site of pain, over acupuncture points orover muscle bellies surrounding tissue. It deliversa biphasic exponentially decaying wave of longpulse duration (16 ms) with pulse frequencieslimited to either 2 pps or 60 pps. Marketing mate-rial argues that frequencies above 60 pps are not

needed because HWT uses a bipolar waveformand 60 pps equates to 120 pps monophasic wave-forms, although this rationale appears to be weakbecause most standard TENS devices deliveringbiphasic waveforms offer frequencies beyond 200pps. Manufacturers also recommend that high-frequency HWT (i.e., 60 pps) generating a strongbut comfortable electrical paraesthesia within thesite of pain will provide the best pain relief. Themechanism of action of this effect is likely to besimilar to that found for conventional TENS.Low-frequency HWT (i.e., 2 pps) generatingmuscle twitches is recommended for in�amma-tion and oedema because it will produce musclepumping actions that will compress surroundingcirculatory vessels and improve blood �ow and�uid drainage.

Clinical studies on HWT are few. It was shownto reduce pain associated with peripheral neu-ropathy in 31 patients with type 2 diabetes whencompared with sham stimulation.194 HWT wasadministered to the lower extremities for 30 mindaily for four weeks using pulses with a frequencyof 2 pps ‘or greater’ and a duration of 4 ms. Afollow-up study reported that HWT improvedneuropathic pain associated with diabetes in 76%of respondents to a postal questionnaire,although this study failed to include a controlgroup.195 Workers have reported that HWTincreases the mechanical pain threshold196 andreduces McGill Pain Questionnaire scores forexperimentally-induced ischaemic pain in healthypeople when compared with sham HWT,197

although this latter �nding was not con�rmed ina follow-up study.198 HWT was also shown toincrease the latency of the compound actionpotential in the super�cial radial nerve of 32healthy volunteers, suggesting that it reducesnerve conduction in peripheral nerves.199 HWTdelivered at 2 pps, but not 60 pps, has also beenshown to increase skin blood �ow and skin tem-perature when compared with placebo, providingindirect evidence that it may be useful in facili-tating tissue repair through improved circula-tion.200

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DiscussionIt is hardly surprising that confusion exists aboutthe effectiveness of TENS and TENS-like deviceswith such an array of available stimulators andclaims of ef�cacious treatment protocols. Thetheoretical principles underpinning many of theTENS-like devices described in this review havetheir traditional roots in physiotherapy and reha-bilitation medicine. Until recently, treatmentwith many TENS-like devices could be obtainedonly under the supervision of a trained therapistin a clinic setting and working under the con-straints of the clinical rota. Advances in elec-tronic technology have reduced the cost, size anddangers of TENS-like devices and companiesnow market to a broader section of health careprofessionals. Increasing numbers of cheap hand-held devices have placed greater emphasis onself-treatment and the general public can pur-chase many TENS-like devices directly frommanufacturers. It is important that the interestsof the public, patients and health care profes-sionals are protected by scrutinizing claims madeby manufacturers about the relative effectivenessof the different devices.

The �ndings of systematic reviews and meta-analyses on the effectiveness of TENS for painrelief can be summarized as follows: TENS willrelieve pain associated with knee osteoarthritis65

and primary dysmenorrhoea,64 but will notrelieve postoperative pain42 or labour pain.50,51

Evidence is inconclusive for poststroke shoulderpain58 and chronic pain in general.57 Evidence forthe ef�cacy of TENS in chronic low back pain hasproduced con�icting results.60–63 These clinicalbottom lines are particularly attractive to practi-tioners when making decisions about treatmentinterventions. However, the term TENS encom-passes a range of output characteristics, applica-tion procedures and dosing regimens, and this hasresulted in the use of inconsistent and sometimesinappropriate criteria to differentiate types ofTENS, such as conventional TENS and AL-TENS.

Furthermore, the evaluation models used insome reviews have been challenged. Trials in theacute pain setting use pain scores as the primaryoutcome measure, despite patients having accessto additional analgesic drugs, which will compro-mise pain scores because patients in both sham

and active TENS groups will titrate analgesicconsumption to achieve effective relief andminimal pain. Analgesic consumption would bethe most clinically meaningful outcome in thesetrials, although this has been dismissed as beingof secondary importance by some authors.51 Thecorrect way to administer TENS is also con-tentious and some systematic reviews includeRCTs that used protocols that underdose or useTENS-like devices that differ from standardTENS devices. When these issues are taken intoaccount they can change the outcome of system-atic reviews.48

An evaluation of the literature on the effec-tiveness of TENS-like devices revealed that:

� Available experimental evidence is limited inboth quality and quantity.

� Controlled studies for different TENS-likedevices, when available, suggest that somehave absolute effectiveness resulting from theelectrical currents rather than from the act ofadministering the currents. However, this is farfrom proven and seems to depend on the typeof nerve �bre activated, irrespective of theoutput characteristics of the device.

� Available evidence suggests that there areminimal differences in the magnitude and timecourse of pain relief achieved with differenttypes of device. Any potential differences inoutcome appear to be linked to the type of�bre activated rather than the output charac-teristics of the device.

� The speci�city of effect of different TENS-likedevices is questioned.

The relationship between output char-acteristics and physiological intentionElectrical currents form the active ingredient ofTENS in much the same way as a chemical struc-ture forms the active ingredient of a drug. In thisreview, output characteristics were the main cri-teria used to differentiate standard TENS devicesfrom nonstandard TENS-like devices. Most ofthe broad categories of TENS-like devices usenovel electrical currents to gain identity in themarket place. Current waveform is commonlyused in marketing literature to differentiate onetype of device from another and all broad cate-gories of devices (i.e., standard TENS, IFT,MET, HVPC) gain identity in part from their


Pain Reviews 2001; 8: 121–158

current waveform (Figure 8). A more appropri-ate way to differentiate devices would be accord-ing to the physiological intention of the currents.When used to generate pain relief, two mainintentions dominate the literature: �rst, the useof currents to assist physiological processes asso-ciated with tissue healing; and secondly, the useof currents to stimulate nerve �bres in order toactivate pain modulatory circuits.

The main intention of microampere currents isto activate cellular processes that assist tissuehealing. Experimental evidence suggests thatMET can alter ATP and other biochemicalmarkers of tissue healing in vitro.100,110–112

However, there is doubt about whether this

translates to meaningful changes in the rate oftissue healing in animals and humans.119 Theabsence of MET-induced sensations such as elec-trical paraesthesia during stimulation suggeststhat MET currents have insuf�cient energy toactivate cutaneous afferents to any appreciableextent. It is assumed that putative pain relieffrom MET is an indirect result of acceleratedtissue healing.

The main intention of milliampere currents isto stimulate neural circuitry directly to modulatenociceptive transmission at peripheral, segmentaland extrasegmental levels. Experimental evi-dence supports the view that recruitment of dif-ferent populations of �bres leads to different

Standard TENS

IFT

HVPC

HWT

APS

Codetron

(a) (b) (c) (d)

Figure 8

Limoge currents

+0-

+0-

+0-

+0-

+0-

+0-

+0-

Figure 8 Waveform characteristics commonly used by standard TENS and TENS-like devices. StandardTENS devices often use pulse waveforms that are monophasic (a), symmetrical biphasic (b), asymmetricalbiphasic (c), or spike-like biphasic (d). IFT uses an amplitude-modulated interference wave resulting from thecollision of two out-of-phase sinusoidal-like currents. HVPC uses high-voltage double spike pulses. Limogecurrents are wave trains of positive pulses of high intensity, short duration, followed by negative pulses ofweak intensity long duration. Codetron uses biphasic square pulses. APS uses a monophasic square pulsewith exponential decay. HWT uses bipolar exponentially decaying pulsed currents. No diagramatic representa-tion of MET or TSE could be found in the literature. Whether these subtle differences in waveform character-istics translate into clinically different outcomes is not known.

150 MI Johnson

Pain Reviews 2001; 8: 121–158

modulatory mechanisms becoming active.Activation of large diameter cutaneous afferents(i.e., Ab) is related to segmental analgesia.Activation of small diameter muscle afferents(i.e., Group III) through a phasic muscle twitchis related to extrasegmental analgesia. Activationof small diameter cutaneous afferents (i.e., Ad)is related to counterirritant effects and blockadeof transmission in peripheral nociceptive nerves.Whether these various mechanisms result in clin-ically meaningful differences in outcome remainscontentious. Theoretical models based onstrength-duration curves for axonal excitationprovides information about the relationshipbetween output characteristics and �bre recruit-ment. However, the simplest way to recruit dif-ferent �bre types is to raise current amplitudeand/or alter electrode positions. This raises ques-tions about the in�uence of other output charac-teristics in determining the magnitude and pro�leof segmental analgesia. The literature lacks pub-lished systematic investigations into the analgesiceffects of different output characteristics (such aspulse frequency, pattern and duration) whencurrent amplitude is kept constant. It has beensuggested that patients choose pulse frequenciesand patterns for reasons of comfort rather thanimproved analgesia.

The physiological justi�cation for incorporat-ing novel output characteristics in many TENS-like devices is weak. Explanations of therelationship between output characteristics andphysiological effect are often general anddescriptions of ‘closing pain gates’ or ‘ increasinglevels of circulating endorphins’ are prevalent inmanufacturers’ literature. It was often dif�cult toascertain whether a TENS-like device was beingadministered with a view to activating nerve�bres selectively or to aid the healing process, orboth. If the TENS-like devices are ‘closing thepain gate’, then it may be cheaper to use a stan-dard TENS device. Clearly, manufacturers needto demonstrate that TENS-like devices produceeffects that are clinically different to, or greaterin magnitude than, those achieved using a stan-dard TENS device. At present, many differencesin output characteristics between TENS-likedevices appear to be purely cosmetic.

The diversity of ways in which electrical cur-rents can be administered confounds categoriza-

tion and the synthesis of available evidence.Electrode sites may be similar to those proposedfor conventional TENS (i.e., around the site ofpain for IFT and HWT) or completely different(i.e., on the head for TCES or spinal cord place-ment for TSE). Treatment regimens varied con-siderably and some seem to defy logic. Forexample, in one trial, APS was administered for16 minutes followed by a 3-minute rest and afurther 16 minutes.185 Intermittent stimulation ofbetween 20 and 60 minutes repeated a few timesa day tended to predominate in published advicefor many TENS-like devices, especially for non-potable devices that reside in clinics. It is possi-ble that such dosing regimens have developedbecause they �t into the clinical rota.73

Patients who use conventional TENS areencouraged to administer treatment to produce astrong, comfortable electrical paraesthesia when-ever they are in pain because this re�ects activ-ity in Ab afferents. Evidence from animals,normal people and patients shows that the effectsof conventional TENS are maximal when thedevice is switched on and are usually short livedonce it is switched off.15,17–19 Intermittent dosingregimens for conventional TENS are known tolead to inadequate treatment and this has beenrecognized as a design �aw in many TENStrials.56,57 When TENS-like devices are used togenerate a strong but comfortable electricalparaesthesia within the site of pain (e.g., HWT,IFT) a continuous dosing regimen should beused. The intermittent dosing regimens recom-mended for TENS-like devices need to be justi-�ed by demonstrating, through well-designedexperimental trials, that poststimulatory effectsactually occur.

The relationship between output characteristics and clinical effectivenessFrom a practical perspective, health care profes-sionals need experimental evidence on absoluteeffectiveness (e.g., against a placebo control) andrelative effectiveness (e.g., against other existingtreatments) to inform clinical decisions. With anever-increasing number of TENS and TENS-likedevices available on the market, evidence aboutrelative effectiveness is particularly important toinform device selection. In essence, health care


Pain Reviews 2001; 8: 121–158

professionals want to know whether changing theoutput characteristics of TENS devices altersclinical effects. Cost-effectiveness should also beconsidered and whether putative treatmenteffects can be achieved by using a standard TENSdevice rather than a more expensive TENS-likedevice. At present, there are few comparativestudies between standard TENS and TENS-likedevices or between different types of TENS-likedevices. Those that exist suggest that the outputcharacteristics of TENS-like devices, which maydiffer from each other markedly, do not in�uenceclinical outcome to the extent inferred by theiradvocates. Clinical trials that examine the rela-tive effectiveness of TENS-like devices with astandard TENS device are desperately needed toinform therapists about device selection.

In conclusion, despite the technologicallyimpressive appearance of many TENS-likedevices, a standard TENS device probablyremains the best type of stimulator for pain relief.Standard TENS devices are predominantly usedto stimulate different populations of nerve �bres,with the potential to produce different analgesicoutcomes. Clinical evidence does suggest that astandard TENS device, if used appropriately, canprovide pain relief. The �ndings of systematicreviews suggesting that TENS is not effective forpostoperative and labour pain have recently beenchallenged. Health care professionals often turnto TENS-like devices when patients fail torespond to treatment with a standard TENSdevice. It is important that the causes of nonre-sponse to standard TENS have been fullyexplored before the switch is made to a moreexpensive TENS-like device. Patients can beinappropriately labelled as nonrespondersbecause they have been given unrealistic expec-tations of treatment outcome or insuf�cient infor-mation about the principles and practice ofTENS use. Experimenting with the electricalcharacteristics, electrode positions or dosingregimen and/or trials of the different types ofTENS, such as AL-TENS, can often overcomeproblems associated with treatment resistantpatients.

The driving force for the design of manyTENS-like devices has been the ability to incor-porate technologically impressive output charac-teristics based on hypothetical and speculative

physiological rationale. At present there is a lackof good quality physiological and clinical evi-dence to justify so many different types of device.In future it would be more relevant to de�neTENS and TENS-like devices according to thephysiological intention of the currents. Physio-logical justi�cation for the inclusion of speci�coutput characteristics in stimulator design shouldalso be provided by manufacturers and supportedby experimental evidence that demonstrateseffects over and above those seen with a standardTENS device. Describing and de�ning TENSeffects in relation to nerve activity will improveconsistency in reporting and will enable system-atic reviews to include and exclude trials accord-ing to the physiological consequences of currentsrather than output characteristics.

References1 Walsh D. TENS. Clinical applications and related

theory. New York: Churchill Livingstone, 1997.2 Johnson M. Transcutaneous electrical nerve

stimulation (TENS). In: Kitchen S ed.Electrotherapy: evidence-based practice. Edinburgh:Churchill Livingstone, 2001: 259–86.

3 Chabal C, Fishbain DA, Weaver M, Heine LW.Long-term transcutaneous electrical nervestimulation (TENS) use: impact on medicationutilization and physical therapy costs. Clin J Pain1998; 14: 66–73.

4 Bandolier. Transcutaneous electrical nervestimulation (TENS) in postoperative pain.Bandolier 1999; (July). Available from: URL:http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Other/AP019.html [Accessed 16-Jan-03]

5 Bandolier. Transcutaneous electrical nervestimulation (TENS) in labour pain. Bandolier 1999;(July). Available from: URL:http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/labour/AP001.html [Accessed 16-Jan-03]

6 Bandolier. Transcutaneous electrical nervestimulation (TENS) in chronic pain. Bandolier 1999;(July). Available from: URL:http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Chronrev/Other/CP074.html [Accessed 16-Jan-03]

7 Woolf C, Thompson J Segmental afferent �bre-induced analgesia: transcutaneous electrical nervestimulation (TENS) and vibration. In: Wall P,Melzack R eds. Textbook of pain. Edinburgh:Churchill Livingstone, 1994: 1191–208.

8 American Physical Therapy Association.Electrotherapeutic terminology in physical therapy:Report by the Electrotherapy Standards Committeeof the Section on Clinical Electrophysiology of the

152 MI Johnson

Pain Reviews 2001; 8: 121–158

American Physical Therapy Association (APTA).Alexandria, VA: APTA, 1990.

9 Sjölund B, Eriksson M, Loeser J. Transcutaneousand implanted electric stimulation of peripheralnerves. In: Bonica J ed. The management of pain.Philadelphia, PA: Lea and Febiger, 1990: l852–61.

10 Johnson MI. A critical review of the analgesiceffects of TENS-like devices. Phys Ther Rev 2001;6: 153–73.

11 Demmink J. The effect of a biological conductingmedium on the pattern of modulation anddistribution in a two-circuit static interferential �eld[Abstract]. In: Abstracts of the Proceedings of the12th International Conference of the WorldConfederation for Physical Therapy; 1995;Washington DC; 583.

12 Demmink J. The degree of modulation ininterferential current stimulation as used inphysiotherapy. The effect of a biological conductingmedium on the pattern of modulation in a two-circuit static interferential �eld [Thesis]. Norway:University of Bergen; 1993.

13 Mannheimer J, Lampe G. Clinical transcutaneouselectrical nerve stimulation. Philadelphia, PA: FADavis, 1988.

14 Johnson MI, Ashton CH, Bous�eld DR, ThompsonJW. Analgesic effects of different pulse patterns oftranscutaneous electrical nerve stimulation on cold-induced pain in normal subjects. J Psychosom Res1991; 35: 313–21.

15 Johnson MI, Ashton CH, Thompson JW. An in-depth study of long-term users of transcutaneouselectrical nerve stimulation (TENS). Implicationsfor clinical use of TENS. Pain 1991; 44: 221–29.

16 Johnson MI, Ashton CH, Thompson JW. Analgesiceffects of acupuncture-like TENS on cold pressorpain in normal subjects. Eur J Pain 1992; 13:101–108.

17 Garrison DW, Foreman RD. Decreased activity ofspontaneous and noxiously evoked dorsal horn cellsduring transcutaneous electrical nerve stimulation(TENS). Pain 1994; 58: 309–15.

18 Garrison DW, Foreman RD. Effects oftranscutaneous electrical nerve stimulation (TENS)on spontaneous and noxiously evoked dorsal horncell activity in cats with transected spinal cords.Neurosci Lett 1996; 216: 125–28.

19 Johnson MI, Tabasam G. A double blind placebocontrolled investigation into the analgesic effects ofinterferential currents (IFC) and transcutaneouselectrical nerve stimulation (TENS) on cold inducedpain in healthy subjects. Physiother Theory Pract1999; 15: 217–33.

20 Sjölund BH. Peripheral nerve stimulationsuppression of C-�ber-evoked �exion re�ex in rats.Part 1: Parameters of continuous stimulation. JNeurosurg 1985; 63: 612–16.

21 Sjölund BH. Peripheral nerve stimulation

suppression of C-�ber-evoked �exion re�ex in rats.Part 2: Parameters of low-rate train stimulation ofskin and muscle afferent nerves. J Neurosurg 1988;68: 279–83.

22 Johnson MI, Ashton CH, Bous�eld DR, ThompsonJW. Analgesic effects of different frequencies oftranscutaneous electrical nerve stimulation on cold-induced pain in normal subjects. Pain 1989; 39:231–36.

23 Walsh D. TENS. Clinical applications and relatedtheory. New York: Churchill Livingstone, 1997:63–81.

24 Walsh D. TENS. Clinical applications and relatedtheory. New York: Churchill Livingstone, 1997:83–124.

25 Johnson MI, Ashton CH, Thompson JW. Theconsistency of pulse frequencies and pulse patternsof transcutaneous electrical nerve stimulation(TENS) used by chronic pain patients. Pain 1991;44: 231–34.

26 Johnson MI. The analgesic effects and clinical useof acupuncture-like TENS (AL-TENS). Phys TherRev 1998; 3: 73–93.

27 Andersson SA, Hansson G, Holmgren E, RenbergO. Evaluation of the pain suppressing effect ofdifferent frequencies of peripheral electricalstimulation in chronic pain conditions. Acta OrthoScand 1976; 47: 149–57.

28 Eriksson MB, Sjölund BH. Acupuncture-likeelectroanalgesia in TNS resistant chronic pain. In:Zotterman Y ed. Sensory functions of the skin.Oxford: Pergamon Press, 1976: 575–81.

29 Andersson SA, Ericson T, Holmgren E, Linquist G.Electroacupuncture. Effect of pain thresholdmeasured with electrical stimulation of teeth. BrainRes 1973; 63: 393–96.

30 Sjölund BH, Terenius L, Eriksson M. Increasedcerebrospinal �uid levels of endorphins afterelectro-acupuncture. Acta Physiol Scand 1977; 100:382–84.

31 Sjölund BH, Eriksson MB. The in�uence ofnaloxone on analgesia produced by peripheralconditioning stimulation. Brain Res 1979; 173:295–301.

32 Meyerson B. Electrostimulation procedures: effectspresumed rationale, and possible mechanisms. In:Bonica J, Lindblom U, Iggo A eds. Advances inpain research and therapy, vol. 5. New York: Raven,1983: 495–534.

33 Walsh DM. Transcutaneous electrical nervestimulation and acupuncture points. ComplementaryTher Med 1996; 4: 133–37.

34 Melzack R, Vetere P, Finch L. Transcutaneouselectrical nerve stimulation for low back pain. Acomparison of TENS and massage for pain andrange of motion. Phys Ther 1983; 63: 489–93.

35 Jeans M, Relief of chronic pain by brief, intensetranscutaneous electrical stimulation - a double


Pain Reviews 2001; 8: 121–158

blind study. In: Bonica J, Liebeskind J, Albe-Fessard D eds. Advances in pain research andtherapy, vol. 3. New York: Raven Press, 1979;601–606.

36 Levin M, Hui-Chan C. Conventional andacupuncture-like transcutaneous electrical nervestimulation excite similar afferent �bers. Arch PhysMed Rehabil 1993; 74: 54–60.

37 Ignelzi RJ, Nyquist JK. Direct effect of electricalstimulation on peripheral nerve evoked activity:implications in pain relief. J Neurosurg 1976; 45:159–65.

38 Ignelzi RJ, Nyquist JK. Excitability changes inperipheral nerve �bers after repetitive electricalstimulation. Implications in pain modulation. JNeurosurg 1979; 51: 824–33.

39 Chung JM, Fang ZR, Hori Y, Lee KH, Willis WD.Prolonged inhibition of primate spinothalamic tractcells by peripheral nerve stimulation. Pain 1984; 19:259–75.

40 Woolf CJ, Mitchell D, Barrett GD, Antinociceptiveeffect of peripheral segmental electrical stimulationin the rat. Pain 1980; 8: 237–52.

41 Carrol EN, Badura AS. Focal intense brieftranscutaneous electric nerve stimulation fortreatment of radicular and postthoracotomy pain.Arch Phys Med Rehabil 2001; 82: 262–64.

42 Carroll D, Tramer M, McQuay H, Nye B, MooreA. Randomization is important in studies with painoutcomes: systematic review of transcutaneouselectrical nerve stimulation in acute postoperativepain. Br J Anaesth 1996; 77: 798–803.

43 Hymes A, Raab D, Yonchiro E, Nelson G, PrintyA. Electrical surface stimulation for control of postoperative pain and prevention of ileus. Surg Forum1974; 65: 1517–20.

44 Schuster G, Infante M. Pain relief after low backsurgery: the ef�cacy of transcutaneous electricalnerve stimulation. Pain 1980; 8: 299–302.

45 Ali J, Yaffe C, Serrette C. The effect oftranscutaneous electric nerve stimulation onpostoperative pain and pulmonary function. Surgery1981; 89: 507–12.

46 Reeve J, Menon D, Corabian P. Transcutaneouselectrical nerve stimulation (TENS): a technologyassessment. Int J Technol Assess Health Care 1996;12: 299–324.

47 Benedetti F, Amanzio M, Casadio C et al. Controlof postoperative pain by transcutaneous electricalnerve stimulation after thoracic operations. AnnThorac Surg 1997; 63: 773–76.

48 Bjordal J, Johnson M, Ljunggren A.Transcutaneous electrical nerve stimulation (TENS)can reduce postoperative analgesic consumption. Ameta-analysis with assessment of optimal treatmentparameters for postoperative pain. Eur J Pain 2003;7: 181–188.

49 Augustinsson L, Bohlin P, Bundsen P et al. Pain

relief during delivery by transcutaneous electricalnerve stimulation. Pain 1977; 4: 59–65.

50 Carroll D, Moore A, Tramer M, McQuay H.Transcutaneous electrical nerve stimulation doesnot relieve in labour pain: updated systematicreview. Contemp Rev Obstet Gynaecol 1997; 9:195–205.

51 Carroll D, Tramer M, McQuay H, Nye B, MooreA. Transcutaneous electrical nerve stimulation inlabour pain: a systematic review. Br J ObstetGynaecol 1997; 104: 169–75.

52 Johnson MI. Transcutaneous electrical nervestimulation (TENS) in the management of labourpain: the experience of over ten thousand women.Br J Midwifery 1997; 5: 400–405.

53 Harrison R, Woods T, Shore M, Mathews G,Unwin A. Pain relief in labour using transcutaneouselectrical nerve stimulation (TENS). ATENS/TENS placebo controlled study in two paritygroups. Br J Obstet Gynaecol 1986; 93: 739–46.

54 Champagne C, Papiernik E, Thierry JP, Noviant Y.[Transcutaneous cerebral electric stimulation byLimoge current during labor.] Ann Fr AnesthReanim 1984; 3: 405–13.

55 Wattrisse G, Leroy B, Dufossez F, Bui Huu Tai R.[Transcutaneous electric stimulation of the brain: acomparative study of the effects of its combinationwith peridural anesthesia using bupivacaine-fentanylduring obstetric analgesia.] Cah Anesthesiol 1993;41: 489–95.

56 McQuay H, Moore A. TENS in chronic pain. In:McQuay H, Moore A eds. An evidence-basedresource for pain relief. Oxford: Oxford UniversityPress, 1998: 207.

57 Carroll D, Moore RA, McQuay HJ, Fairman F,Tramer M, Leijon G. Transcutaneous electricalnerve stimulation (TENS) for chronic pain[Cochrane review]. In: The Cochrane Library, Issue4, 2001; Oxford: Update Software.

58 Price CI, Pandyan AD. Electrical stimulation forpreventing and treating post-stroke shoulder pain: asystematic Cochrane review. Clin Rehabil 2001; 15:5–19.

59 Price CI, Pandyan AD. Electrical stimulation forpreventing and treating post-stroke shoulder pain[Cochrane review]. In: The Cochrane Library, Issue4, 2001; Oxford: Update Software.

60 Milne S, Welch V, Brosseau L et al. Transcutaneouselectrical nerve stimulation (TENS) for chronic lowback pain [Cochrane Review]. In: The CochraneLibrary, Issue 4, 2001; Oxford: Update Software.

61 Brosseau L, Milne S, Robinson V et al. Ef�cacy ofthe transcutaneous electrical nerve stimulation forthe treatment of chronic low back pain: a meta-analysis. Spine 2002; 27: 596–603.

62 Gadsby JG, Flowerdew MW. Transcutaneouselectrical nerve stimulation and acupuncture-liketranscutaneous electrical nerve stimulation for

154 MI Johnson

Pain Reviews 2001; 8: 121–158

chronic low back pain [Cochrane review]. In: TheCochrane Library, Issue 2, 2000; Oxford: UpdateSoftware.

63 Flowerdew M, Gadsby G, A review of thetreatment of chronic low back pain withacupuncture-like transcuatenous electrical nervestimulation and transcutaneous electrical nervestimulation. Comp Ther Med 1997; 5: 193-201.

64 Proctor ML, Smith CA, Farquhar CM, Stones RW,Transcutaneous electrical nerve stimulation andacupuncture for primary dysmenorrhoea (CochraneReview). In: The Cochrane Library, Issue 1, 2002;Oxford: Update Software.

65 Osiri M, Welch V, Brosseau L et al. Transcutaneouselectrical nerve stimulation for knee osteoarthritis.(Cochrane review). In: The Cochrane Library, Issue1, 2002; Oxford: Update Software.

66 Palmer ST, Martin DJ. Interferential current forpain control. In: Kitchen S ed. Electrotherapy:evidence based practice. Edinburgh: ChurchillLivingstone, 2001: 287–300.

67 Pope GD, Mockett SP, Wright JP. A survey ofelectrotherapeutic modalities: Ownership and use inthe NHS in England. Physiotherapy 1995; 81: 82–91.

68 Robertson VJ, Spurritt D. Electrophysical agents:implications of their availability and use inundergraduate clinical placements. Physiotherapy1998; 84: 335–44.

69 DeDomenico G. New dimensions in interferentialtherapy. A theoretical and clinical guide. Lin�eld:Reid Medical, 1987.

70 Savage B. Interferential therapy. London: Wolfe,1992.

71 Nikolova L. Treatment with interferential current.Edinburgh: Churchill Livingstone, 1987.

72 Martin D. Interferential for pain control. In:Kitchen S, Bazin S eds. Clayton’s Electrotherapy,tenth edition. London: Saunders, 1994: 306–15.

73 Johnson MI. The mystique of interferentialcurrents. Physiotherapy 1999; 85: 294–97.

74 Johnson MI, Tabasam G. A questionnaire surveyon the clinical use of interferential currents (IFC)by physiotherapists [Abstract]. In: Abstract of theProceedings of the Pain Society of Great BritainAnnual Conference; April 1998; Leicester; abstr 29.

75 Ganne J, Speculand B, Mayne L, Goss A.Inferential therapy to promote union of mandibularfractures. Aust N Z J Surg 1979; 49: 81–83.

76 Laycock J, Green R. Interferential therapy in thetreatment of incontinence. Physiotherapy 1988; 74:161–68.

77 Nelson B. Interferential therapy. Aust J Physiother1981; 27: 53–56.

78 Willie CD. Interferential therapy. Physiotherapy1969; 55: 503–505.

79 Kloth LC. Interference current. In: Nelson RM,Currier DP eds. Clinical electrotherapy . EastNorwalk, CT: Appleton and Lange, 1991: 221–60.

80 Noble JG, Lowe AS, Walsh DM. Interferentialtherapy review: Part 1. Mechanism of analgesicaction and clinical use. Phys Ther Rev 2000; 5:239–45.

81 Tabasam G, Johnson MI. Electrotherapy for painrelief: does it work? A laboratory based study toexamine the analgesic effects of electrotherapy oncold-induced pain in healthy individuals. Clin EffectNurs 1999; 3: 14–24.

82 Johnson MI, Tabasam G. A single-blind placebo-controlled investigation into the analgesic effects ofinterferential currents on experimentally inducedischaemic pain in healthy subjects. Clin PhysiolFunct Imaging 2002; 22: 187–96.

83 Johnson MI, Tabasam G. A single-blindinvestigation into the hypoalgesic effects ofdifferent swing patterns of interference currents(IFC) on cold-induced pain in healthy volunteers.Arch Phys Med Rehabil (in press).

84 Johnson MI, Tabasam G. Differential analgesiceffects of amplitude modulated wave frequencies ofinterferential currents (IFC) on cold induced painin healthy subjects [Abstract]. In: Abstract of theProceedings of the IXth World Congress on Pain.1999 Aug 22–27; Vienna, Austria. Seattle: IASPPress, 1999: 453.

85 Noble JG. Interferential therapy: assessment ofhypoalgesic and neurophysiological effects [Thesis].Belfast: University of Ulster, 2000.

86 Taylor K, Newton RA, Personius WJ, Bush FM.Effects of interferential current stimulation fortreatment of subjects with recurrent jaw pain. PhysTher 1987; 67: 346–50.

87 Quirk A, Newman RJ, Newman KJ. An evaluationof interferential therapy, shortwave diathermy andexercise in the treatment of osteoarthrosis of theknee. Physiotherapy 1985; 71: 55–57.

88 Werners R, Pynsent PB, Bulstrode CJ. Randomizedtrial comparing interferential therapy withmotorized lumbar traction and massage in themanagement of low back pain in a primary caresetting. Spine 1999; 24: 1579–84.

89 Hurley DA, Minder PM, McDonough SM, WalshDM, Moore AP, Baxter DG. Interferential therapyelectrode placement technique in acute low backpain: a preliminary investigation. Arch Phys MedRehabil 2001; 82: 485–93.

90 Palmer ST, Martin DJ, Steedman WM, Ravey J,Alteration of interferential current andtranscutaneous electrical nerve stimulationfrequency: effects on nerve excitation. Arch PhysMed Rehabil 1999; 80: 1065–71.

91 Picker R, Micro electrical neuromuscularstimulation. Network-Electrix 1987; (March):S72–S74.

92 Picker R. Current trends: low volt pulsed microampstimulation parts 1 and 2. Clin Man Phys Ther 1988;9: 10–33.


Pain Reviews 2001; 8: 121–158

93 Mercola JM, Kirsch DL. The basis for microcurrentelectrical therapy in conventional medical practice.J Adv Med 1995; 8(2). Available from: URL:http://www.harborside.com/naspenmed/page8.htm[Accessed 15-Jan-03]

94 Kirsch DL, Lerner FN. Electromedicine: The otherside of physiology. In: Weiner R ed. The Textbookof the America Academy of Pain Management,Innovations in pain management: a practical guidefor clinicians, vol. 4 update. Winter Park, FL: GRPress, 1995. Available from: URL:http://www.alternatives.com/raven/cpain/chap23-0.html [Accessed 15-Jan-03]

95 DuPont JS, Graham R, Tidwell JB. Trigger pointidenti�cation and treatment with microcurrent.Cranio 1999; 17: 293–96.

96 Heffernan MS. Comparative effects of microcurrentstimulation on EEG spectrum and correlationdimension. Integrative Physiol Behav Sci 1996; 31:202–209.

97 Becker R, Selden G. The body electric . New York:Morrow, 1985.

98 Becker R, Murray D. Method for producing cellulardedifferentiation by means of very small electricalcurrents. Trans N Y Acad Sci 1967; 29: 606–15.

99 Watson T. Electrical stimulation for wound healing:a review of current knowledge. In: Kitchen S ed.Electrotherapy: evidence-based practice, eleventhedition. Edinburgh: Churchill Livingstone, 2002:313–34.

100 Cheng N, Hoof HV, Bockx E. The effects ofelectric current on ATP generation, proteinsynthesis, and membrane transport in rat skin. ClinOrthop Rel Res 1982; 171: 264–72.

101 Seegers JC, Engelbrecht CA, van Papendorp DH.Activation of signal-transduction mechanisms mayunderlie the therapeutic effects of an appliedelectric �eld. Med Hypotheses 2001; 57: 224–30.

102 Weber MD, Servedio FJ, Woodall WR. The effectsof three modalities on delayed onset musclesoreness. J Orthop Sports Phys Ther 1994; 20:236–42.

103 Lambert MI, Marcus P, Burgess T, Noakes TD.Electro-membrane microcurrent therapy reducessigns and symptoms of muscle damage. Med SciSports Exerc 2002; 34: 602–607.

104 Johnson MI, Penny P, Sajawal MA. Anexamination of the analgesic effects of microcurrentstimulation (MES) on cold-induced pain in healthysubjects. Physiother Theory Pract 1997; 13: 293–301.

105 Lerner F, Kirsch D. A double blind comparativestudy of micro-stimulation and placebo effect inshort term treatment of the chronic back painpatient. J Chiropract 1981; 15: 101–106.

106 Branco K, Naeser MA. Carpal tunnel syndrome:clinical outcome after low-level laser acupuncture,microamps transcutaneous electrical nervestimulation, and other alternative therapies – an

open protocol study. J Altern Complement Med1999; 5: 5–26.

107 Annal N, Soundappan S, Palaniappan K,Chandrasekar S. Introduction of transcutaneous,low voltage, non-pulsatile direct current (DC)therapy for migrane and chronic headaches. Acomparison with transcutaneous electrical nervestimulation (TENS). Headache Q 1992; 3: 434–37.

108 Bertolucci LE, Grey T. Clinical comparative studyof microcurrent electrical stimulation to mid-laserand placebo treatment in degenerative joint diseaseof the temporomandibular joint. Cranio 1995; 13:116–20.

109 Wolcott L, Wheeler P, Hardwicke H, Rowley B.Accelerated healing of skin ulcers byelectrotherapy. South Med J 1969; 62: 795–801.

110 Nessler J, Mass D. Direct-current electricalstimulation of tendon healing in vitro. Clin OrthopRel Res 1987; 217: 303–12.

111 Oweye I, Spielholz N, Fetto J, Nelson J. Low-intensity pulsed galvanic current and the healing oftenotomized rat achilles tendons: preliminary reportusing load-to-breaking measurements. Arch PhysMed Rehabil 1987; 68: 415–18.

112 Richez J, Chamay A, Bieler L. Bone changes dueto pulses of direct electric microcurrent. VirchowsArch A Pathol Anat 1972; 357: 11–18.

113 Seegers JC, Lottering ML, Joubert AM et al. Apulsed DC electric �eld affects P2-purinergicreceptor functions by altering the ATP levels in invitro and in vivo systems. Med Hypotheses 2002; 58:171–76.

114 Rowley BA. Electrical current effects on E. coligrowth rates. Proc Soc Exp Biol Med 1972; 139:929–34.

115 Rowley BA, McKenna JM, Chase GR, Wolcott LE.The in�uence of electrical current on an infectingmicroorganism in wounds. Ann N Y Acad Sci 1974;238: 543–51.

116 Rowley BA, McKenna JM, Wolcott LE.Proceedings: The use of low level electrical currentfor enhancement of tissue healing. Biomed SciInstrum 1974; 10: 111–14.

117 Leffmann D, Arnall D, Holmgren P, Cornwall M.Effect of microamperage stimulation on the rate ofwound healing in rats. A histological study. PhysTher 1994; 74: 195–200.

118 Byl NN, McKenzie AL, West JM et al. Pulsedmicroamperage stimulation: a controlled study ofhealing of surgically induced wounds in Yucatanpigs. Phys Ther 1994; 74: 201–13.

119 Rothstein J. Microamperage: a lesson to be learned[editors note]. Phys Ther 1994; 74: 194.

120 Assimacopoulos D. Low intensity negative electriccurrent in the treatment of ulcers of the leg due tochronic venous insuf�ciency. Preliminary report ofthree cases. Am J Surg 1968; 115: 683–87.

121 Gault W, Gatens P. Use of low intensity direct

156 MI Johnson

Pain Reviews 2001; 8: 121–158

current in management of ischemic skin ulcers.Phys Ther 1976; 56: 265–69.

122 Sinitsyn L, Razvozva E. [Effects of electricalmicrocurrents on regeneration processes in skinwounds.] Ortop Travmatol Protez 1986; Feb (2):25–28 (Rus).

123 Carley P, Wainapel S. Electrotherapy foracceleration of wound healing: low intensity directcurrent. Arch Phys Med Rehabil 1985; 66: 443–46.

124 Mulder G. Treatment of open-skin wounds withelectric stimulation. Arch Phys Med Rehabil 1991;72: 375–77.

125 Feedar JA, Kloth LC, Gentzkow GD. Chronicdermal ulcer healing enhanced with monophasicpulsed electrical stimulation. Phys Ther 1991; 71:639–49.

126 Gardner SE, Frantz RA, Schmidt FL. Effect ofelectrical stimulation on chronic wound healing: ameta-analysis. Wound Repair Regen 1999; 7:495–503.

127 Low J, Reed A. Electrical stimulation of nerve andmuscle. In: Low J, Reed A eds. Electrotherapyexplained: principles and practice. Oxford:Butterworth-Heinemann, 1994: 39–116.

128 Bjordal JM. Electrical currents. In: Bjordal JM,Johnson MI, Couppe C eds. Clinical electrotherapy.Your guide to optimal treatment. Kristiansand:HoyskoleForlaget Norwegian Academic Press, 2001:102–16.

129 Johannsen F, Gam A, Hauschild B, Mathiesen B,Jensen L. Rebox: an adjunct in physical medicine?Arch Phys Med Rehabil 1993; 74: 438–40.

130 Hatten E, Hervik J, Kalheim T, Sundvor T. Paintreatment with Rebox. Fysioterapeuten 1990; 11:8–13.

131 Nussbaum EL, Gabison S. Rebox effect onexercise-induced acute in�ammation in humanmuscle. Arch Phys Med Rehabil 1998; 79: 1258–63.

132 Khan J. Electrical stimulation. In: Khan J ed.Principles and practice of electrotherapy . New York:Churchill Livingstone, 1987: 95–125.

133 Kloth LC, Feedar JA. Acceleration of woundhealing with high voltage, monophasic, pulsedcurrent. Phys Ther 1988; 68: 503–508.

134 Grif�n JW, Tooms RE, Mendius RA, Clifft JK,Vander Zwaag R, el-Zeky F. Ef�cacy of highvoltage pulsed current for healing of pressure ulcersin patients with spinal cord injury. Phys Ther 1991;71: 433–42.

135 Jette D. Effect of different forms of transcutaneouselectrical nerve stimulation on experimental pain.Phys Ther 1986; 66: 187–93.

136 Morris L, Newton RA. Use of high voltage pulsedgalvanic stimulation for patients with levator anisyndrome. Phys Ther 1987; 67: 1522–25.

137 Asbjorn O. Treatment of tennis elbow withtranscutaneous nerve stimulation (TNS). Availablefrom: URL: http://www.paingone.com/ 2000

[Accessed 01-Jul-02]138 Ivanova-Stoilova T, Howells D. The usefulness of

PainGone pain killing pen for self-treatment ofchronic musculoskeletal pain - a pilot study[Abstract]. In: The Pain Society of Great BritainAnnual Scienti�c Meeting Abstracts; 2002 Apr 9–12;Bournemouth, UK; abstr. 104.

139 Kirsch DL, Smith RB. The use of cranialelectrotherapy stimulation in the management ofchronic pain: a review. NeuroRehabilitation 2000;14: 85–94.

140 Limoge A, Robert C, Stanley TH. Transcutaneouscranial electrical stimulation (TCES): a review 1998.Neurosci Biobehav Rev 1999; 23: 529–38.

141 Southworth S. A study of the effects of cranialelectrical stimulation on attention andconcentration. Integrative Physiol Behav Sci 1999;34: 43–53.

142 Taylor D, Lee C, Katims J. Effects of cranialtranscutaneous electrical nerve stimulation innormal subjects at rest and during psychologicalstress. Acupunct Electrother Res 1991; 16: 65–74.

143 Schroeder MJ, Barr RE. Quantitative analysis ofthe electroencephalogram during cranialelectrotherapy stimulation. Clin Neurophysiol 2001;112: 2075–83.

144 Stinus L, Auriacombe M, Tignol J, Limoge A, LeMoal M. Transcranial electrical stimulation withhigh frequency intermittent current (Limoge’s)potentiates opiate-induced analgesia: blind studies.Pain 1990; 42: 351–63.

145 Robert C, Limoge A, Stinus L. Transcranialelectrical stimulation (Limoge’s currents)potentiates the inhibition of righting re�ex inducedby droperidol in rats. Brain Res 1999; 822: 132–41.

146 Alantar A, Azerad J, Limoge A, Robert C, RokytaR, Pollin B. Potentiation of fentanyl suppression ofthe jaw-opening re�ex by transcranial electricalstimulation. Brain Res 1997; 763: 14–20.

147 Malin DH, Lake JR, Hamilton RF, Skolnick MH.Augmented analgesic effects of enkephalinaseinhibitors combined with transcranialelectrostimulation. Life Sci 1989; 44: 1371–76.

148 Auriacombe M, Tignol J, Le Moal M, Stinus L.Transcutaneous electrical stimulation with Limogecurrent potentiates morphine analgesia andattenuates opiate abstinence syndrome. BiolPsychiatry 1990; 28: 650–56.

149 Mignon A, Laudenbach V, Guischard F, Limoge A,Desmonts JM, Mantz J. Transcutaneous cranialelectrical stimulation (Limoge’s currents) decreasesearly buprenorphine analgesic requirements afterabdominal surgery. Anesth Analg 1996; 83: 771–75.

150 Stanley TH, Cazalaa JA, Atinault A, Coeytaux R,Limoge A. Louville Y, Transcutaneous cranialelectrical stimulation decreases narcoticrequirements during neurolept anesthesia andoperation in man. Anesth Analg 1982; 61: 863–66.


Pain Reviews 2001; 8: 121–158

151 Stanley TH, Cazalaa JA, Limoge A, Louville Y.Transcutaneous cranial electrical stimulationincreases the potency of nitrous oxide in humans.Anesthesiology 1982; 57: 293–97.

152 Svetlov V, Alisov A, Kozlov S, Tsibuliak V.[Central electroanalgesia as a component ofcombined anesthesia in reconstructivemicrosurgery]. Anesteziol Reanimatol 1994; 4: 46–50(Rus).

153 Mantz J, Azerad J, Limoge A, Desmonts JM.Transcranial electrical stimulation with Limoge’scurrents decreases halothane requirements in rats.Evidence for the involvement of endogenousopioids. Anesthesiology 1992; 76: 253–60.

154 Solomon S, Elkind A, Freitag F et al. Safety andeffectiveness of cranial electrotherapy in thetreatment of tension headache. Headache 1989; 29:445–50.

155 Smith RB, Tiberi A, Marshall J. The use of cranialelectrotherapy stimulation in the treatment ofclosed-head-injured patients. Brain Inj 1994; 8:357–61.

156 Winick RL. Cranial electrotherapy stimulation(CES): a safe and effective low cost means ofanxiety control in a dental practice. Gen Dent 1999;47: 50–55.

157 Scherder EJ, Deijen JB, Vreeswijk SH, SergeantJA, Swaab DF. Cranial electrostimulation (CES) inpatients with probable Alzheimer’s disease. BehavBrain Res 2002; 128: 215–17.

158 Klawansky S, Yeung A, Berkey C, Shah N, Phan H,Chalmers TC. Meta-analysis of randomizedcontrolled trials of cranial electrostimulation.Ef�cacy in treating selected psychological andphysiological conditions. J Nerv Ment Dis 1995; 183:478–84.

159 Limoge A. [Electricity in pain management.] PresseMedicale 1999; 28: 2197–203 [Fre].

160 Bates JA, Nathan PW. Transcutaneous electricalnerve stimulation for chronic pain. Anaesthesia1980; 35: 817–22.

161 Loeser J, Black R, Christman A. Relief of pain bytranscutaneous electrical nerve stimulation. JNeurosurg 1975; 42: 308–14.

162 Eriksson MB, Sjölund BH, Nielzen S. Long termresults of peripheral conditioning stimulation as ananalgesic measure in chronic pain. Pain 1979; 6:335–47.

163 Tulgar M, McGlone F, Bowsher D, Miles JB.Comparative effectiveness of different stimulationmodes in relieving pain. Part II. A double-blindcontrolled long-term clinical trial. Pain 1991; 47:157–62.

164 Tulgar M, McGlone F, Bowsher D, Miles JB.Comparative effectiveness of different stimulationmodes in relieving pain. Part I. A pilot study. Pain1991; 47: 151–55.

165 Ekstrom U, Sjölund B. Is modulation the way to

increase the ef�cacy of conventional TENS? Anexperimental study. In: Dubner R, Gebhart G,Bond MR eds. Proceedings of the Vth WorldCongress on Pain (Pain research and clinicalmanagement, vol. 3); 1987 Aug 2–7; Hamburg.Amsterdam: Elsevier, 1988: 583–89.

166 Pomeranz B, Niznick G. Codetron, a newelectrotherapy device overcomes the habituationproblems of conventional TENS devices. Am JElectromed 1987; (�rst quarter): 22–26.

167 Herman E, Williams R, Stratford P, Fargas-BabjakA, Trott M. A randomized controlled trial oftranscutaneous electrical nerve stimulation(CODETRON) to determine its bene�ts in arehabilitation program for acute occupational lowback pain. Spine 1994; 19: 561–68.

168 Fargas-Babjak A, Rooney P, Gerecz E.Randomized trial of Codetron for pain control inosteoarthritis of the hip/knee. Clin J Pain 1989; 5:137–41.

169 Fargas Babjak AM, Pomeranz B, Rooney PJ.Acupuncture-like stimulation with codetron forrehabilitation of patients with chronic painsyndrome and osteoarthritis. Acupunct ElectrotherRes 1992; 17: 95–105.

170 Cheng R, Pomeranz B. Electrotherapy of chronicmusculoskeletal pain; comparison ofelectroacupuncture and acupuncture-like TENS.Clin J Pain 1986; 2: 143–49.

171 Macdonald ARJ, Coates TW. The discovery oftranscutaneous spinal electroanalgesia and its reliefof chronic pain. Physiotherapy 1995; 81: 653–60.

172 Royle J. Transcutaneous spinal electroanalgesia(TSE) and its ef�cacy on GP consultation rates[Abstract]. In: The Pain Society of Great BritainAnnual Scienti�c Meeting Abstracts; Bournemouth,UK; 2002 Apr 9–12; abstr. 121.

173 Royle J. Transcutaneous spinal electroanalgesia(TSE) and its ef�cacy in the patient community: aqualitative assessment [Abstract]. In: The PainSociety of Great Britain Annual Scienti�c MeetingAbstracts; Bournemouth UK; 2002 Apr 9–12: abstr.122.

174 Leem J, Park E, Paik K. Electrophysiologicalevidence for the antinociceptive effect oftranscutaneous electrical stimulation onmechanically evoked responsiveness of dorsal hornneurons in neuropathic rats. Neurosci Lett 1995;192: 197–200.

175 Gopalkrishnan P, Sluka KA. Effect of varyingfrequency, intensity, and pulse duration oftranscutaneous electrical nerve stimulation onprimary hyperalgesia in in�amed rats. Arch PhysMed Rehabil 2000; 81: 984–90.

176 Sluka KA, Bailey K, Bogush J, Olson R, RickettsA. Treatment with either high or low frequencyTENS reduces the secondary hyperalgesia observedafter injection of kaolin and carrageenan into the

158 MI Johnson

Pain Reviews 2001; 8: 121–158

knee joint. Pain 1998; 77: 97–102.177 Sluka KA, Judge MA, McColley MM, Reveiz PM.

Low frequency TENS is less effective than highfrequency TENS at reducing in�ammation-inducedhyperalgesia in morphine-tolerant rats. Eur J Pain2000; 4: 185–93.

178 Towell A, Williams D, Boyd S. High frequencynon-invasive stimulation over the spine: effects onmood and mechanical pain tolerance in normalsubjects. Behav Neurol 1997; 10: 61–65.

179 Hilberstadt D, Barlas P, Foster N. The effect oftranscutaneous spinal electroanalgesia upon chronicpain: a single case study. Physiotherapy 2000; 86:150–51.

180 Heffernan A, Rowbotham D. Transcutaneous spinalelectroanalgesia: its effects in acute and chronicpain patients and healthy volunteers [Abstract]. In:The Pain Society of Great Britain Annual Scienti�cMeeting Abstracts; Bournemouth, UK; 2002 Apr9–12: abstr. 53.

181 Robb K. Pain after breast cancer treatment: arandomised, placebo controlled crossover trial tocompare two different stimulation analgesictechniques. In: The Pain Society of Great BritainAnnual Scienti�c Meeting Abstracts; Leicester, UK;1998 Apr: abstr. 45.

182 Berger P, Matzner L. Study on 99 patients withosteoarthritis (OA) of the knee to investigate theeffectiveness of low frequency electrical currents onmobility and pain: action potential simulationtherapy (APS) current compared withtranscutaneous electrical nerve stimulation (TENS)and placebo. South Afr J Anaesthesiol Analg 1999;5: 1–11.

183 Papendorp V, Krugere M, Maritz C, Dippenaar N.Action potential simulation therapy: self assessmentby 285 patients with chronic pain. Geneeskunde TheMedical Journal 2000; (Jan/Feb): 18–24.

184 Sandham J. Action potential simulation therapy.Eng Technol 2000; (July): 45–48.

185 Odendaal C, Joubert G. APS therapy – a new wayof treating chronic headache – a pilot study. SouthAfr J Anaesthesiol Analg 1999; 5: 1–3.

186 Noble JG. Interferential therapy: assessment ofhypoalgesic and neurophysiological effects . [Thesis].Belfast: University of Ulster, 2000: 166–87.

187 Wet ED, Oosthuizen J, Odendaal C, Shipton E.Neurochemical mechanisms that may underlie theclinical ef�cacy of ‘action potential simulation’(APSim) therapy in chronic pain management.South Afr J Anaesthesiol Analg 1999; 5: 1–5.

188 Facchinetti F, Sandrini G, Petraglia F, Alfonsi E,Nappi G, Genazzani AR. Concomitant increase innociceptive �exion re�ex threshold and plasma

opioids following transcutaneous nerve stimulation.Pain 1984; 19: 295–303.

189 Facchinetti F, Sforza G, Amidei M et al. Centraland peripheral beta-endorphin response totranscutaneous electrical nerve stimulation. NIDARes Monogr 1986; 75: 555–58.

190 Johnson MI, Ashton CH, Thompson JW, WeddellA, Wright Honari S. The effect of transcutaneouselectrical nerve stimulation (TENS) andacupuncture on concentrations of beta endorphin,met enkephalin and 5 hydroxytryptamine in theperipheral circulation. Eur J Pain 1992; 13: 44–51.

191 Alves-Guerreiro J, Noble JG, Lowe AS, WalshDM. The effect of three electrotherapeuticmodalities upon peripheral nerve conduction andmechanical pain threshold. Clin Physiol 2001; 21:704–11.

192 Alvaro M, Kumar D, Julka IS. Transcutaneouselectrostimulation: emerging treatment for diabeticneuropathic pain. Diabetes Technol Ther 1999; 1:77–80.

193 Meizels P. Electronic anesthesia. H-wave and TMJtreatment. J California Dent Assoc 1987; 15: 42–44.

194 Kumar D, Marshall HJ. Diabetic peripheralneuropathy: amelioration of pain withtranscutaneous electrostimulation. Diabetes Care1997; 20: 1702–705.

195 Julka IS, Alvaro M, Kumar D. Bene�cial effects ofelectrical stimulation on neuropathic symptoms indiabetes patients. J Foot Ankle Surg 1998; 37:191–94.

196 McDowell BC, McCormack K, Walsh DM, BaxterDG, Allen JM. Comparative analgesic effects of H-wave therapy and transcutaneous electrical nervestimulation on pain threshold in humans. Arch PhysMed Rehabil 1999; 80: 1001–1004.

197 Walsh DM, Baxter D, Allen JM, Bell AJ, MokhtarB. An assessment of the analgesic effects of H-wavetherapy upon experimentally-induced ischaemicpain [Abstract]. Ir J Med Sci 1992; 161: 472.

198 McDowell BC, Lowe AS, Walsh DM, Baxter GD,Allen JM. The lack of hypoalgesic ef�cacy of H-wave therapy on experimental ischaemic pain. Pain1995; 61: 27–32.

199 McDowell BC, Lowe AS, Walsh DM, Baxter GD,Allen JM. The effect of H-wave therapy uponconduction in the human super�cial radial nerve invivo. Exp Physiol 1996; 81: 821–32.

200 McDowell BC, McElduff C, Lowe AS, Walsh DM,Baxter GD. The effect of high- and low-frequencyH-wave therapy upon skin blood perfusion:evidence of frequency-speci�c effects. Clin Physiol1999; 19: 450–57.

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