ulsed radiofrequency energy (PRFE) has mul-tiple medical applications including pain mod-ulation, wound healing, and bone repair.1,2 PRFE refers to a noninvasive, nonthermal method of delivering nonionizing electro-magnetic energy to a targeted area with a fre-quency ranging from 1 to 1000 Hz. The pul-

satile delivery, with bursts lasting from 10 µsec to 1 msec, allows for dissipation of heat making this method non-abla-tive. The FDA has cleared such shortwave diathermy devices for adjunctive use in the palliative treatment of postoperative pain and edema in superficial soft tissue.3,4

Mechanisms for proposed analgesia include modulating calcium and calmodulin pathways,5 increasing endogenous opioid precursor mRNA,6 altering transcription of cytokine and matrix metalloprotease levels,7 increasing chondrocyte proliferation,8 and enhancing noradrenergic and serotoner-gic descending inhibitory pain pathways.9 However the exact mechanism is still not completely understood at this time.

There are several studies that have demonstrated some effectiveness with PRFE. In a recent meta-analysis of 16 controlled trials, 11 trials with PRFE had positive outcomes and 5 trials with neutral outcomes that were measured across different pain conditions.3 There were 2 double blind random-ized controlled trial that showed PRFE was more effective than sham in shoulder pain and knee osteoarthritis.10,11 Additionally

other trials and case series have shown PRFE to provide signif-icant pain reduction in chronic back pain, non-specific wrist pain, plantar fasciitis, and postoperative pain.12-15

The role and effectiveness of PRFE in treating various chronic pain conditions is still being defined, and it is unclear if certain conditions fail to respond. Additionally there is very little literature detailing whether treating beyond 4 weeks is beneficial. Our goal for performing this review was to determine whether PRFE was beneficial for chronic pain and if additional benefit occurred with those who received 8 week treatment.

Study Method and DesignThe objective of this observational series was to record the effects and duration of PRFE treatment across various pain syndromes. A retrospective analysis was performed via chart review on 40 patients in an outpatient Veteran’s Affairs (VA) Physical Medicine and Rehabilitation Clinic in Long Beach, California. Internal Review Board (IRB) approval was attained through the Southern California Institute for Research and Education before collecting any data. Inclusion criteria com-prised of every patient that received PRFE treatment within the principal investigator’s patient population at the VA.

Eligible patients were required to demonstrate chronic pain unrelieved by a recent procedure or injection. Exclusion crite-ria comprised of any patient who did not take a PRFE device home after the initial office trial. It should be noted that the treating physician did not offer this treatment to anyone with active infection, cancer, or an implantable electronic stimu-lating device.

Patients prescribed PRFE were first offered an outpatient initial trial of transcutaneous PRFE. A treatment applicator pad was placed directly over the site of maximal pain and a nonionizing, nonthermal carrier frequency energy was emit-ted at 27.12 MHz for 30 minutes. The pulsed RF (pulsed width 42 µsec, pulse frequency 1 kHZ) has a predicted elec-trical field strength of 591 V/m at 5 cm above the applicator.

After receiving the trial, patients were then instructed to take the PRFE device home to use twice daily for 30 minutes. Patients were then instructed to return to the clinic within 4 weeks to evaluate their pain and activities of daily living (ADL). If the patient’s pain improved but their ADL had not, they had the option to extend their trial for an addi-tional 4 weeks.

The reviewer collected each subject’s medical diagnosis as determined by radiographs, laboratory results, and clinical judgment. Numeric pain scores were also collected via chart review, which included pain before initial trial (initial), 30 minutes after trial (post-trial), 4 weeks, and 8 weeks. This was scored on a numeric rating scale of 0-10 with 0 reflecting no

P

Pulsed Radiofrequency Energy for Treatment of Chronic Pain SyndromesRetrospective case series finds reduced pain scores following PRFE treatments.

Ravi G. Mirpuri, DOPhysical Medicine and RehabilitationUniversity of California, Irvine Medical CenterOrange, California

Patricia W. Nance, MDPhysical Medicine and RehabilitationUniversity of California, Irvine Medical CenterOrange, California

PRACTICAL PAIN MANAGEMENTThe Nation’s Premier Teaching Journal for Pain Practitioners

1Reprint from October 2015 | Pract icalPainManagement.com650-0178-00 A

pain, 1-3 mild pain and mild interfer-ence on ADL, 4-6 moderate pain and moderate interference on ADL, and 7-10 severe pain and inability to per-form ADL.

Study Results Forty subjects met inclusion crite-ria, and no patient was excluded due to trial failure. Therefore 40 patients completed the initial trial, which was reduced to 36 subjects at 4 weeks and 21 subjects at 8 weeks. Patient drop-out occurred for various reasons: pain resolved with treatment, twice daily fre-quency was inconvenient, insufficient efficacy, and patient inability to access electricity to run device. It is import-ant to note that no subject was reported to discontinue treatment secondary to adverse side effects.

Numeric pain scores were averaged for each stage of the study (7.9 initial, 5.7 post trial, 4.6 at 4 weeks, and 3.0 at 8 weeks), which showed consistent reduction of pain over time (Figure 1). Statistical analysis using the Wilcox Signed Rank Test for a nonparametric

two-tailed test was performed across the 40 patients. Results showed that the post-trial, 4 weeks, and 8 weeks average pain scores were all statistically reduced compared to initial pain scores (P<0.001). Additionally, there was sta-tistical improvement from post-trial to 4 weeks (P<0.006), which was main-tained without further change from 4 weeks to 8 weeks

The data was analyzed by patient diagnosis. Each of the patients treated had at least one diagnosis and 3 patients met criteria for two diagno-ses that explained their pain symptoms (eg, spinal stenosis and lumbar radic-ulopathy). As a result, the 40 patients had a total of 43 diagnoses after being grouped into the following categories: rotator cuff tear, failed back syndrome, myofascial pain, radiculopathy, spinal stenosis, diabetic neuropathy, knee osteoarthritis, lumbar facet arthritis, ankle osteoarthritis, and postsurgical abdominal pain (Table 1).

Due to the low sample sizes, statisti-cal significance of the diagnoses was not reported to prevent false comparisons.

Nevertheless, all 10 diagnoses showed a generalized trend of improvement over time with few exceptions: slight wors-ening of failed back syndrome from post-trial to 4 weeks, no change in dia-betic neuropathy during post-trial to 8 weeks, no change in knee osteoarthri-tis at 4 and 8 weeks, and some worsen-ing of postsurgical abdominal pain at 8 weeks (Figure 2, page 4). However it should be noted that these exceptions occurred only in diagnoses with low sample sizes of 3 or less, but regard-less all diagnoses showed improvement from their initial pain scores.

PRFE Reduces PainAlthough conclusions are limited by the observational nature of this review, the data demonstrates that PRFE was clinically and statistically effective in reducing pain over time for up to 4 weeks. There was no statistically sig-nificant further reduction of pain after 4 weeks, but maintenance of analgesia was preserved. It should be noted that only patients who benefited at 4 weeks could be eligible for 8 weeks treatment.

When performing a literature review for the average length of PRFE treat-ment, there is inconsistent dura-tions ranging from a single session to 6 weeks.3,4 In a 6 week study by Foley-Nolan et al, significant improvement in persistent neck pain was seen at both 3 and 6 weeks.16 In our specific study, we provided no evidence of improve-ment from PRFE beyond 4 weeks treat-ment other than maintenance of cur-rent levels of analgesia.

Despite the low sample sizes when comparing numeric pain scores based on diagnosis, every patient showed improvement from baseline with PRFE treatment. Therefore we have no rec-ommendation against trialing PRFE for the following conditions: rota-tor cuff tear, failed back syndrome, myofascial pain, radiculopathy, spinal stenosis, diabetic neuropathy, knee

PRFE Overall EffectivenessFor Pain

Effect of PRFE Based on Diagnosis

Treatment Time

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Initial

Post Trial

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8 weeks

Initial(n=40)

Post-Trial(n=40)

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8 weeks(n=21)

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Figure 1. This graph compares the numeric pain scores at each stage of the treatment. Statistical analysis using the Wilcox Signed Rank Test for a nonparametric two-tailed test showed that the post-trial, 4 weeks, and 8 week average pain scores were reduced compared to initial pain (P<0.001). Also there was statistical improvement from post-trial to 4 weeks (P<0.006), but there was no statistical change from 4 to 8 weeks. There were 40 patients at the beginning of the study. Dropouts occurred at week 4 (n=36) and week 8 (n=21) for multiple reasons, including early resolution of symptoms, lack of significant relief, noncompliance, and other miscellaneous reasons.PRFE, pulsed radiofrequency energy

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osteoarthritis, lumbar facet arthritis, ankle osteoarthritis, and postsurgical abdominal pain. Additionally this fur-thers evidence that PRFE is effective in treating chronic pain conditions. Future studies should be considered to analyze a larger patient population that received PRFE in order to per-form large scale statistical comparisons across diagnoses.

In our review, none of the 40 patients were reported to have a treatment related adverse event. This corresponds with other literature reviews that have not reported any adverse effects related to PRFE. Regardless there still is a gen-eral consensus to avoid usage in patients who have the following: implanted leads, cardiac rhythm devices, preg-nancy, malignancy, and joints of immature bone development.3,17,18 In our study, patients were required to fail conventional therapies such as physical therapy, corticosteroid injec-tions, orthotics, and pharmacologic

treatments. Due to the limited side effect profile, PRFE may be a great alternative for those who failed con-ventional treatment.

Since PRFE treatment is considered relatively painless and easy to use at home, this approach provides a nonsur-gical option for chronic pain manage-ment. There still is uncertainty about the duration of analgesia beyond 8 weeks, which we hope to follow in a future study. It would be beneficial for future studies to determine whether PRFE is needed daily like transcu-taneous electrical nerve stimulation (TENS) device, or whether it has a long lasting analgesic effect after treatment is discontinued. One study already com-pared TENS to percutaneous pulsed radio frequency and found no differ-ence in treating shoulder pain, but this approach varies significantly from the PRFE approach.19 Thus, it would be beneficial to compare TENS and PRFE in a future study.

SummaryPRFE treatment is an approach in chronic pain management that may be useful across a variety of diagnoses. In our observational study, patients continued to improve in pain up to 4 weeks, but further studies are needed to determine an appropriate duration of treatment. This nonsurgical approach is considered relatively safe and could be considered in patients who fail con-ventional therapies. It is also relatively easy to use at home and not reported to have sedating effects like opioids. Our study has several limitations including a relatively low sample size, retrospec-tive analysis, and lack of control com-parison. Nonetheless we feel our find-ings combined with previous literature results suggest that PRFE is an effective option to treat chronic pain.

Authors’ Bios: Ravi Mipuri, DO, is Chief Resident in Physical Medicine & Rehabilitation at the University

Table 1. Analysis of Diagnosis and Average Numeric Pain Scores During Each Stage of Trial

Diagnosis Initial NPS Post-Trial NPS 4-weeks NPS 8-weeks NPS

Rotator Cuff Tear 9 (n=7) 6.7 (n=7) 5.7 (n=5) 2.8 (n=3)

Failed Back Syndrome 9 (n=2) 7.5 (n=2) 7.8 (n=2) 3.5 (n=1)

Myofascial 7.8 (n=6) 5.7 (n=6) 4.5 (n=6) 3.7 (n=3)

Radiculopathy 7.6 (n=11) 5.3 (n=11) 5.0 (n=11) 2.2 (n=5)

Spinal Stenosis 7.9 (n=6) 6.6 (n=6) 5.0 (n=5) 4.0 (n=2)

Diabetic Neuropathy 7.0 (n=1) 5.0 (n=1) 5.0 (n=1) 5.0 (n=1)

Knee Osteoarthritis 8.0 (n=3) 6.3 (n=3) 4.3 (n=2) 4.3 (n=2)

Lumbar Facet Arthritis 8.3 (n=4) 6.1 (n=4) 4.5 (n=4) 4.0 (n=2)

Ankle Osteoarthritis 7.0 (n=2) 3.8 (n=2) 2.0 (n=2) 1.3 (n=2)

Postsurgical Abdominal Pain

6.0 (n=1) 3.0 (n=1) 0.0 (n=1) 2.5 (n=1)

Total # of Subject Diagnoses

n=43 n=43 n=39 n=22

n, number of diagnoses during each stage of the experiment; NPS, numeric pain scoreNote: The number of diagnoses may be more than the number of patients in the study; some patients had more than one pain diagnosis.

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of California, Irvine. He received his Doctorate in Osteopathy from Lake Erie College of Osteopathic Medicine in 2011.

Patricia W. Nance, MD, is currently Chief of Rehabilitation Services at the VA Long Beach Healthcare System and

a Clinical Professor in the Department of Physical Medicine & Rehabilitation at the University of California, Irvine. She received medical degree from the South Florida University in Tampa in 1980. She completed her postgraduate

medical training and residency in Physical Medicine & Rehabilitation at Dalhousie University, in 1984. Her research inter-ests have included neurophysiology (spinal and cortical evoked potentials and physio-logical quantification of spasticity), neuro-pharmacology (particularly involving the management of spasticity), chronic pain, and gait enhancement strategies.

The authors have disclosed that they have no competing interests. There are no per-sonal or financial disclosures to report in the context of this study.

AcknowledgementsThe authors would like to acknowledge both Departments of PM&R at the University of California, Irvine and Long Beach VA Healthcare system in allowing physician resources to be used in develop-ing this study. IRB approval was attained through the Southern California Institute for Research and Education (Project #1301).

References

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2. Ritz MC, Gallegos R, Canham MB, Eskalai M, George FR. PROVANT Wound-Closure System accelerates closure of pressure wounds in a randomized, double-blind, placebo-controlled trial. Ann NY Acad Sci. 2002;961:356-359.

3. Guo L, Kubat NJ, Nelson TR, Isenberg RA. Meta-analysis of clinical efficacy of pulsed radio frequency energy treatment. Ann Surg. 2012;255(3):457-467.

4. Moffett J, Kubat NJ, Isenberg RA. Pulsed radio frequency energy as an effective pain treatment. Pract Pain Manage. 2011;11(3):71-73.

5. Pilla AA. Electromagnetic fields instantaneously modulate nitric oxide signaling in challenged biological systems. Biochem Biophys Res Commun. 2012;426(3):330-333.

6. Moffett J, Fray LM, Kubat NJ. Activation of endogenous opioid gene expression in human keratinocytes and fibroblasts by pulsed radio- frequency energy fields. J Pain Res. 2012;5: 347-357.

7. Moffett J, Kubat NJ, Griffine NE, Ritz MC, George FR. Pulsed radio frequency energy field treat-ment of cells in culture: Increased expression

of genes involved in angiogenesis and tissue remodeling during wound healing. J Diabetic Foot Complications. 2011;3(2):30-39.

8. Fitzsimmons RJ, Gordon SL, Kronberg J, Ganey T, Pilla AA. A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling. J Orthop Res. 2008;26(6):854-859.

9. Hagiwara S, Iwasaka H, Takeshima N, Noguchi T. Mechanisms of analgesic action of pulsed radio- frequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. Eur J Pain. 2009;13(3):249-252.

10. Taverner M and Loughnan T. Transcutaneous pulsed radiofrequency treatment for patients with shoulder pain booked for surgery: a double-blind, randomized controlled trial. Pain Pract. 2014;14(2):101-108.

11. Taverner M G, Ward TL, Loughnan TE. Transcu-taneous pulsed radiofrequency treatment in pa-tients with painful knee awaiting total knee joint replacement. Clin J Pain. 2010;26(5):429-432.

12. Balogh SE. Transcutaneous application of pulsed radiofrequency: four case reports. Pain Pract. 2004;4(4):310-313.

13. Michel R. Use of pulsed radio frequency energy in the effective treatment of recalcitrant plantar fasciitis: Six case histories. Foot (Edinb). 2012;22(1):48-52.

14. Heden P and Pilla A. Effects of pulsed elec-tromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients. Aesthetic Plast Surg. 2008;32(4):660-666.

15. Shandles ID, Pruchniewski J, Reynolds KL. Heel neuroma: the enigma of recalcitrant heel pain and an innovative approach highlighting sixty surgical cases and a review of two hundred and fifty seven symptomatic but non-surgical cases. The Foot. 2002;12(1):10-20.

16. Foley-Nolan D, Barry C, Coughlan RJ, O’Connor P, Roden D. Pulsed high frequency (27MHz) electromagnetic therapy for persistent neck pain. A double blind, placebo-controlled study of 20 patients. Orthopedics. 1990;13(4):445-451.

17. Guo L, Kubat NJ, Isenberg RA. Pulsed radio frequency energy (PRFE) use in human medical applications. Electromagn Biol Med. 2011;30(1):21-45.

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19. Korkmaz O K, Capaci K, Eyigor C, Eyigor S. Pulsed radiofrequency versus conventional transcutaneous electrical nerve stimulation in painful shoulder: a prospective, randomized study. Clin Rehabil. 2010;24(11):1000-1008.

PRFE Overall EffectivenessFor Pain

Effect of PRFE Based on Diagnosis

Treatment Time

Diagnosis

Initial

Post Trial

4 weeks

8 weeks

Initial(n=40)

Post-Trial(n=40)

4 weeks(n=36)

8 weeks(n=21)

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Num

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Figure 2. This graph compares and trends the average numeric pain scores at each stage of the treatment based on diagnosis.PRFE, pulsed radiofrequency energy

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