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Two styles of acupuncture for treating painfuldiabetic neuropathy - a pilot randomised control trialAndrew C Ahn, Taher Bennani, Roy Freeman, Osama Hamdy, Ted J Kaptchuk

SummaryIn a pilot study, we evaluated the clinical and mechanistic effects of two styles of acupuncture, TraditionalChinese Medicine (TCM) and Japanese acupuncture, for the treatment of painful diabetic neuropathy. Outof seven patients enrolled, three received Traditional Chinese acupuncture while four received Japanese styleacupuncture. Treatments were delivered once a week for 10 weeks. Acupuncturists were permitted toselect the needle interventions. Substantial differences in diagnostic techniques, choice of acupuncturepoints, and needle manipulation were observed between TCM and Japanese acupuncturists. Clinically,patients allocated to Japanese acupuncture reported decreased neuropathy-associated pain according tothe daily pain severity score, while the group allocated to the TCM acupuncture reported minimal effects.Both acupuncture styles, however, lowered pain according to the McGill Short Form Pain Score, TheTCM style improved nerve sensation according to quantitative sensory testing while the Japanese style hada more equivocal effect. No evident changes were observed in glucose control or heart rate variability in eithergroup.

KeywordsAcupuncture, diabetic neuropathy, Japanese acupuncture. Traditional Chinese Medicine.

Introduction

Diabetic neuropathy, generally considered to be themost symptomatically distressing complication ofdiabetes, affects more than 30% of people withtliabetes,' Unfortunately, no consistently effectivelieatment lor diabetic neuropathy is available andpatients and providers are forced to struggle withmedications that provide only partial relief.̂ Severalsmall studies suggest that acupuncture may providethe needed assistance for pain reduction. Humancase series have demonstrated substantial symptomreduction without added side effects.''' Animal modelshave suggested the anaesthetic and nerve-regenerativecapacities of acupuncture,'* While these preliminarydata offer promise, they are insufficient to providecompelling evidence to adopt acupuncture as aiherapy for diabetic neuropathy.

Proper evaluation of acupuncture for diabeticneuropathy is complicated by two important factors.First, diabetic neuropathy is a complex disea,se withmultiple pathophysiological causes and variable

clinical presentations,' Tt can present with pain orloss of sensation or both. Second, acupuncture stylesare numerous and varied. One style may employ anentirely different technique when compared withanother style. Unless the important details are madeclear from the start, the amalgamation of these twocomplex factors when evaluating acupuncture fordiabetic neuropathy can yield inconsistent results.Relevant factors such as type of acupuncture,physiologic effects, and appropriateness of clinicaloutcome measures should be thoroughly appraised.

The study of acupuncture for diabetic neuropathymay be complex but may also offer an opportunity toevaluate the varied effects of acupuncture ba,sed onstyle and clinical outcome. This pilot study has twoprimary aims: (1) to assess the feasibility of studyingtwo acupuncture styles, Traditional Chinese Medicineand Japanese Kiiko-Matsumoto style acupuncture, fortreatment of painful diabetic neuropathy, and (2) toobtain preliminary data for the clinical andmechanistic effects of acupuncture on diabetic

Andrew C Ahninstructor in medicineHarvard Medical Schooland

Beth Israel DeaconessMedical Center. Boston

MA

Taher Bennaniclinical resi'uniwrJoslin Diabetes CenterBoston. MA

Roy FreemanpntffssorBeth Israel DeaconessMedical Center, BostonMA

Osama Hamdyinslrticu/r in medicineJoslin Diabetes CenterBoston. MA

Ted J Kaptehukussocialc professorHarvard MedicalSchool, Boston, MA

Correspondence:Andrew C Ahn

aahn(S'hnis,harvard,edu

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neuropathy. We hypothesise that TCM and PCiiko-

style Japanese acupuncture have different clinical

and mechanistic effects on diabetic neuropathy.

Methods

Patients were recruited from primary care andspeciality diabetes clinics at Beth Israel DeaconessMedical Center and Joslin Diabetes Center in Boston,Massachusetts from August to November 2004. Paperflyers and pamphlets were regularly placed instrategic areas around the clinic sites. Physicianswere also requested to refer any eligible patient withdiabetic neuropathy.

Patients were considered eligible if they wereover the age of 18 years, had type I or type II diabetes,had experienced pain or tingling in both lowerextremities for more than six months, scored morethan 40 out of 100 on the visual analogue scale ofthe short-form McGill Pain Questionnaire (SF-MPQ),had a score greater than two on the MichiganNeuropathy Screening Instrument (MNSI), and wereacupuncture naive. Patients were excluded if theywere pregnant, or if they had evidence of lowerextremity vascular insufficiency or claudication,neuropathy from other causes, a history ofamputations other than the toes, if they reported useof any investigational drugs within the previous sixmonths, or if they reported changes in painmedications two months before enrolment.

Prior to acupuncture treatments, studyparticipants completed a two week run-in periodrequiring completion of diaries on pain severity, sleepinterference, glucose control, and usage ofmedications. Information was recorded four timesa day, coinciding with times when blood glucoselevels might be checked: before each meal and beforebedtime. The run-in period ensured that participantswere compliant with the diaries and demonstratedsufficient pain attributed to diabetic neuropathy.Individuals who reported more than four observationsof pain greater than four (on the 11 -point Likert scale)within a week were retained in the study. Forqualifying participants, the information acquiredduring the run-in period was used for baselineinformation.

Participants were randomised to two styles ofacupuncture: Japanese style (Kiiko-Matsumoto'sForm) and Traditional Chinese Medicine style. Kiiko-Matsumoto form of Japanese acupuncture was

chosen because of its popularity in the New Englandarea and the availability of classes and textbooksdetailing its principles and techniques,"" Forsimplicity, this style of Japanese acupuncture willherein be referred to simply as Japanese acupuncturewith the caveat that Kiiko-style is one of manyJapanese styles. Acupuncture treatments wereperformed at the Harvard-Thomdike General ClinicalResearch Center at Beth Israel Deaconess MedicalCenter, Treatments were delivered weekly for a totalof 10 treatments. The treatment length and intervalswere detemiined after consulting the acupuncturists.Following a pragmatic treatment protocol,acupuncturists were permitted to treat patients as ifthe patients were being seen in a normal clinicalsetting. However, massage, herbal prescriptions (orany other medical prescription), moxa. cupping, andlifestyle modifying therapies were not allowed.During the study period, study participants wereadvised not to change their pain medications,although changes in acetaminophen use were allowedwith a maximum dose of 3g per day.

The treatment protocol was approved by theinstitutional review boards at Beth Israel DeaconessMedical Center, Joslin Medical Center, and HarvardMedical School.

Three experienced acupuncturists were enlistedin this trial. Two of the acupuncturists had more than20 years of experience and were each considered'Masters' in their respective style of acupuncture(Traditional Chinese and Japanese), The thirdacupuncturist was an experienced Japanese-stylepractitioner (-10 years of experience) who substitutedthe Japanese Master when she was not able to attend.

The primary outcome for the study was the 11-point Likert Scale daily pain severity score. It wasrecorded four times a day and measured the level oi'pain attributed to diabetic neuropathy on a scale of 0to 10 (10 being worst). Due to the dynamic nature ofdiabetic neuropathy symptoms, this measure iscapable of capturing the variations in pain levels andis therefore considered most reflective of patients'pain symptoms by most major studies.'"" Otheroutcome measures obtained from the diaries incltideda sleep interference score (detlned as the amount ofsleep interference due to nocturnal pain), glucosecontrol, and use of pain medication.Other secondary measures were obtained at week 0.week 5, and week 10 after randomisation. These

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measures included the Profile of Mood States scores,the pain rating index portion of SF-MPQ, SF36Quality of Life Questionnaire, and blood tests(including complete blood cell count, creatinine, andhaemoglobin A lC). Quantitative sensory tests basedon cooling and warming sensations were obtainedon both legs at week 0 and week 8 afterrandomisation. To assess for physiologic effects,pLilse wave analysis and heart rate variability wereobtained at weeks 0, 5, and 10 to measure arterialcompliance and autonomic nervous system function,respectively. In addition to these outcome measures,a licensed acupuncturist was present at eachacupuncture treatment to record the interventionsperformed. Recorded variables included diagnostictechniques, number of needles used, acupuncture|ioints selected for needling, manipulation techniqueif any, needling depth, and assessment of treatmentelTicacy,

Because this study was not powered to detectdifferences in outcome between the two styles,comparative statistical analyses were not performed.Data are presented in a descriptive format. Theprimary outcome measure, the daily pain severityscore, was averaged over a seven day period. Foreach treatment arm, the weekly scores were graphedagainst time (in weeks) to describe any time trends.For missing data, the last recorded value was carriedover to the next time point following an intention-to-treat analysis.

Results

The study enrolled seven patients with chronic painful

diabetic neuropathy - three were treated with TCM

acupuncture and four were treated with Japanese

acupuncture. The patient characteristics are shown in

Table 1, All patients reported limited relief with pain

modulating treatments (such as gabapentin) and had

exhausted drug treatment options. Two subjects

reported past enrolment in investigational drug trials.

These participants, in general, had a long history of

diabetes and diabetic neuropathy. The TCM

acupuncture group compared to the Japanese

acupuncture group had poorer glucose control as

documented by the haemoglobin AlC levels. The

Japanese acupuncture group had comparatively

longer duration of diabetes and diabetic neuropathy.

Out of seven study subjects, six fully completed

the 10 weekly treatments. One subject from the

Japanese acupuncture treatment arm left the trial

midway (about six weeks into treatment), citing

worsening of symptoms.

iI

Style differences in interventions '

The treatments delivered by the two acupuncturestyles differed substantially as shown in Table 2.Differences were noted in diagnostic techniques,choice of acupuncture points, and the manner inwhich the needles were handled and manipulated.In general, the TCM style relied on the radial pulse,tongue, and elicitation of tenderness along certain

I Ka,seline characteristics (mean values unless stated)

Characteristics

Age

DM type (number, I/ID

DM duration (yrs)

Neuropathy duration (yrs)

Hj;bAlC(%)

MNSI* (maxitnum score = 8)

Pain Rating Index of the SF-MPQt (maximum score = 45)

Expectancy tor Acupuncture^

TCM acupuncture(n=3)

Mean I range]

63 years 142.79)

0/3

13 18.191

2,811,3,5]

8,817,2.11,5]

3,5 [2,5,5]

19 110,41]

1 10,21

.Japanese acupuncture(n=4)

Mean [range]

58 years 143,fi71

2/2

19 16.321

6,9 11.10]

6,6 [5,7,7,7]

4,1 [3,4,5]

17,8 115.40,51

2,3 12,3]

* Michigan Ncurtipatlw Screeninii instrument I MNSI) assesses the appeiu'ance of feet (calluses, fissures), presence of ulceration, ankleretlex, and vibratory perception of great toe (or other if amputated), A score greater than 2 has both high specificity (95?}) iind sensitivity(8()'/() lor the presence of diabetic neuropathy,r Short-Form McGill Pain Questionnaire (SF-MPQ) Pain Rating Index assesses both the sensory and affective components ofpain using 15 descriptors, each scored from 0 to 3, A higher score indicates more pain,:|: Flxipi'ctamy 4-Likert Scale measures the patient's perceived efficacy of acupuncture in treating his or her pain.

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Table 2 Differences in treatment approach between styles

Aspects of style

Diagnosis

Number of needles used

Acupuncture points used

Needle depth

Manipulation

Therapeutic end point

TCM acupuncture

tongue & pulse

6-14

mostly leg points (ST36, ST40, SP4, SP9,

LR3, KI3, BL22-25)

>25mm

frequent

de qi. pulse

Japanese acupuncture

'reflex points'

18-25

points all over body ('Sphincter ofOddi'.scalp points, 'immune' and 'sugar' points!

<5mni

minitnal or none

release of retlex tenderness

meridians for diagnoses. Compared to the Japanese

style, fewer needles were used, more needles were

localised to the symptom area, needles were inserted

deeper, and they were manipulated more frequently.

The Japanese style relied on the radial pulse as well,

but placed more emphasis on strategic reflex points

- where tenderness could be elicited with pressure

and released by shallow needling at related

acupuncture points.

Diabetic neuropathy-related outcomes

The weekly pain severity scores are charted in Figure1. Individuals in the Japanese Acupuncture group,on the average, noted a greater decrease in painscores, although this difference appeared to diminishwith time.

For the quantitative sensory testing, the TCMacupuncture group noted greater improvement insensation by both cooling and warming comparedto the Japanese group, as charted in Figure 2,Interestingly, both groups noted a decrease in painaccording to the Pain Rating Index of the SF-MPQ,This index measures the pain level using sensoryand affective descriptors and is scaled from 0 to 45(45 being worst). The TCM acupuncture group hada decrease from 19 at week 0 to 14.3 at week 10,while the Japanese Acupuncture group had a decreasefrom 17,8 at week 0 to 13.5 at week 10.

There were no notable differences in changes ofprofile of mood states (POMS) or blood test results,such as white blood cell count, creatinine, andhaemoglobin, with the exception of haemoglobinAlC, The Hgb AlC levels in the TCM acupuncturegroup were consistently elevated at 8.8 (week 0) and9.2 (week 10), whereas the Japanese acupuncturegroup had levels of 6,6 (week 0) and 6,5 (week 10),The weekly blood glucose levels and insulin usage

did not reliably change with acupuncture (Figure 3),

The sleep interference score and SF36 Quality of

Life Questionnaire proved to be either tcx) confusing

or time consuming for the study participants to

complete. As a result, the data could not be

meaningfully analysed.

Physiological markers

The Holter monitor readings showed evidence of

multiple atrial ectopic beats in two of the six subjects

- one from each acupuncture group. Atrial ectopic

beats are found commonly in elderly individuals and

can interfere with heart rate variability analysis - as

it did with these two subjects. For the remaining four

subjects, there were no notable differences in heart

rate variability seen with acupuncture by time-

domain, frequency-domain, and non-linear measures.

The quality of the puLse wave readings proved to be

too poor for adequate interpretation.

Qualitative outcomes

Within the confines of the study protocol, theacupuncturists reportedly did not feel at completeliberty to utilise their full repertoire of treatments.Were it not for these restrictions, the TCMacupuncturist would have used herbal treatmentsand moxa (burning of herb over acupuncture points)while the Japanese acupuncturist would have usedmoxa and electrical or magnetic stimulation. Inaddition, the TCM acupuncturist would have ideallyrecommended visits twice a week rather than once aweek.

The acupuncture treatments were uniformlydescribed as relaxing and comforting. Adjectivescommonly used to describe the sessions included'relaxing', 'skilful', 'comfortable', 'serene', 'calm',and 'warm'. One subject in the Japanese

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Daih' pain severity - Japanesele

vel

Pai

n

6

5

4

1

-2 -1 0

y

2 3 4 5

Week

p.

7 8 9 10

•—Patient n

I - Patient 12

Patient J3

Patient J4

^ 4

Daily pain severity - TCM

\\

• a-•— Patient TCMl

•- Patient TCM2

Patient TCM3

0 1 2 3 4 5 6 7 8 9 lU

Week

I Weekly average of daily pain severity scores by acupuncture style.

0 *-

Quantitative sensoiy testltig

Oweek 8 weeks

Time

-•— Warming - TCM

-• Warming - Japanese

Cooling - TCM

Cooling - Japanese

Figure 2 Quantitative sensory testing: Just noticeable difference' marks a patient's ability to distinguish

a certain sensation at a range of stimulation levels: the lower 'just noticeable difference' score indicates

improved sensation.

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Blood Sugar/Insulin I^evcls

-2 -1 0 1 2 3 4 5 6 7 8 9 lu

-Glucose-TCM

Glucose - Jap

Insulin-TCM

Insulin -Jap

Figure 3 Weekly average of blood glucose and insulin use levels.

acupuncture group described 'cramping whenacupuncturist pressed hard', A subject in the TCMacupuncture group described 'heat going up somesections of legs'. Generally, the subjects randomisedto the TCM acupuncture group reported moresensations ('achiness' and 'warmth') during needlingthan the subjects allocated to the Japaneseacupuncture group.

Discussions after the completion of the trialindicated that four of the six patients would definitelyconsider continuing the acupuncture treatments, ifgiven the option. Three were in the Japaneseacupuncture group and one was in the TCMacupuncture group. One subject in the Japaneseacupuncture group recorded: 'My feet feel muchbetter after the treatment. The circulation is perfect!The bottoms of the feet are not sensitive to the touch.The feet hurt less,' Another subject in the Japaneseacupuncture group summarised: 'The acupuncturehelps tny arthritis as well as lowering my insulinlevel (Hgb AlC), Stress is a major factor in mydiabetes and acupuncture helps me to deal with mystress more effectively. My pain level from myneuropathy has dropped, I do not wake up asfrequently as I did before acupuncture started ,,, Iwill continue with the acupuncture because it hashelped me so much. I was very sceptical at first butI am a believer now.'

Discussion

Based on our observational records, TCM andJapanese acupuncture differed significantly in the

manner in which diagnosis and treatments wereadministered. For clinical outcomes, Japaneseacupuncture lowered neuropathy-associated painaccording to our primary outcome measure (the dailypain severity score) while the TCM acupuncture hadminimal effect. Both styles, however, lowered painaccording to the Pain Rating Index of the SF-MPQ,In addition, the TCM style improved nerve sensationaccording to quantitative sensory testing while theJapanese style had a more equivocal effect. Nonotable differences were seen in glucose control oruse of insulin.

Given the very small sample size, no conclusioncan be drawn about the efficacy of either acupuncturestyle for the treatment of diabetic neuropathy, Alarger study is needed to address this issueappropriately and a placebo control would also becritical. Nevertheless, it is encouraging to ,see thatindividuals with refractory pain noted someimprovement. Decreased pain in the Japaneseacupuncture group, despite including the individualwith worsened symptoms, suggests that acupuncturemay truly be effective for particular individuals withdiabetic neuropathy. Furthermore, the improvedsensations of the TCM acupuncture group as shownby quantitative sensory testing are promising. Ifreplicated in a larger study, TCM acupuncture may beable to do what other medications have failed toconsistently do thus far, namely improve sensation inpersons with diabetic neuropathy.

The differences in treatment techniques andclinical outcomes support the hypothesis that the

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Summary points

A small pilot study in patients with painful diabeticneuropalhy compared traditional Chinese acupuncturewith Japanese acupuncture

Japanese acupuncture was superior according to somemeasures, and Chinese according to others

two acupuncture styles differ in their clinical andmechanistic effects on diabetic neuropathy. Theresults from the study's physiologic markers wereLinable to disclose why these clinical differenceswere observed. In order to fully address thishypothesis, a future .study should have a large enoughsatnple size to confirm these clinical differences andshould also incorporate more physiologic markersthat are wisely chosen and properly administered.Even if this larger study were performed, however, itwould be important not to make broad-basedconclusions. While the techniques and principleswere quite distinct, the two styles of acupunctureused in this study do not fully represent the myriadacupuncture styles available in the clinical setting. Inaddition, because the acupuncturists expressed somerestrictions with the protocol, we cannot concludefully that the study findings accurately reflect theresults seen in real acupuncture treatments.Furthermore, our outcome measures did not mirrorthe very positive sentiments expressed by many of thestudy participants, Hopetully, future studies will beable to elaborate why this discrepancy betweenquantitative and qualitative results can occur.

Acknowledgments

This research was supported by a grant from theDiabetes Action Research and Education Foundationand partially supported by grant number K23-AT(K)3238 of the National Center for ComplementaryAlternative Medicine (NCCAM), Its contents aresolely the responsibility of the authors and do notnece,ssarily represent the official views of the NationalCenter lor Complementary and Altemative Medicine.National Institutes of Health, We thank NIH/NCRRKcsciu'ch Resource for Complex Physiologic Signalsfor assistance in heart rate variability analysis. The

authors would also like to thank Jacqui Fischer and

Sriurai Pooramatikul for their assistance.

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