Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain

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1 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Assessment Program Volume 25, No. 4 November 2010 Executive Summary Background Low-level laser, defined as red-beam or near-infrared lasers with a wavelength between 600 and 1,000 nm and power from mw, has been proposed to have therapeutic effects, particularly for musculoskeletal conditions. Objective This Assessment will review evidence to determine if low-level laser therapy is effective treatment for carpal tunnel syndrome and chronic neck pain. Search Strategy A search of the MEDLINE database (via PubMed) was completed for the period up through May The search strategy used the terms laser or low-level laser as textwords or subject terms. Articles were limited to those published in English language and enrolling human subjects. The MEDLINE search was supplemented by an examination of article bibliographies and relevant review articles, which were searched for citations. Selection Criteria The Assessment was meant to review rigorous clinical trials of low-level laser therapy that had clinically relevant outcomes. Thus, sham-controlled clinical trials that assessed outcomes at least 2 weeks beyond the end of treatment were selected. Main Results For the indication of carpal tunnel syndrome, 4 studies enrolling a total of 151 patients met inclusion criteria. The 4 randomized sham-controlled clinical trials of low-level laser therapy have serious limitations. However, 2 of the 4 studies show statistically significant differences in pain assessed on a VAS scale showing benefit of low-level laser therapy. One of the studies showing benefit had a small sample size of 19 and enrolled patients with rheumatoid arthritis. The other study had limited followup of only 2 weeks beyond the period of treatment. One of the studies that did not show a significant difference between laser and sham treatment had a sample size of only 15. BlueCross BlueShield Association An Association of Independent Blue Cross and Blue Shield Plans For the indication of chronic neck pain, 6 clinical trials enrolling a total of 285 patients met inclusion criteria. The 6 selected studies showed variable results. Two of the 6 studies showed statistically significant findings for the principal outcome of change in VAS pain score. Two studies showed magnitudes of change in VAS pain score consistent with benefit, but were not statistically significant. One of these studies had a small sample size and the other may have had a flawed analysis. Two studies showed similar improvements in pain scores in both laser- and sham-treated control groups and thus resulted in no difference between the treatments. NOTICE OF PURPOSE: TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 1

2 Discussion For carpal tunnel syndrome, none of the 4 studies of low-level laser therapy stands out as particularly methodologically strong so that definitive conclusions can be based on its results. For low-level laser therapy in chronic neck pain, there are numerous differences in patient selection, treatment regimen, and trial co-interventions so that it is not possible to coherently explain the differences in results. Again, no single study is so methodologically strong that it by itself makes a sufficient case for a definitive conclusion regarding the effect of laser therapy. Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether low-level laser therapy for the treatment of carpal tunnel syndrome or chronic neck pain meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate governmental regulatory bodies. Several low-level laser devices have received 510(k) marketing clearance from the U.S. Food and Drug Administration for the clinical indication of carpal tunnel syndrome. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. For the clinical indication of carpal tunnel syndrome, the existing randomized clinical trials are insufficient to make conclusions regarding the effect of low-level laser therapy. The findings of the 4 studies are inconsistent. No one study is so methodologically sound that its results would be definitive. In general, the studies were small and most studies did not follow patients for long periods of time beyond treatment. For the clinical indication of chronic neck pain, the existing randomized clinical trials are insufficient to make conclusions regarding the effect of low-level laser therapy. The findings of the 6 studies are variable. Again, no one study is so methodologically sound that its results would be definitive. In general, the studies were small and most studies did not follow patients for long periods of time beyond treatment. 3. The technology must improve the net health outcome; and 4. The technology must be as beneficial as any established alternatives. The evidence is insufficient to make conclusions regarding whether low-level laser therapy either improves the net health outcome or is as beneficial as any established alternatives for the indications of carpal tunnel syndrome or chronic neck pain. 5. The improvement must be attainable outside the investigational settings. It has not yet been demonstrated whether low-level laser therapy improves health outcomes in the investigational setting. Therefore, it cannot be demonstrated whether improvement is attainable outside the investigational settings. For the above reasons, low-level laser therapy for carpal tunnel syndrome or for chronic neck pain does not meet the TEC criteria Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

3 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Contents Assessment Objective 4 Background 4 Methods 6 Formulation of the Assessment 7 Review of Evidence 7 Discussion 19 Summary of Application of the 19 Technology Evaluation Criteria References 21 Published in cooperation with Kaiser Foundation Health Plan and Southern California Permanente Medical Group. TEC Staff Contributors Author David H. Mark, M.D., M.P.H.; TEC Executive Director Naomi Aronson, Ph.D.; Director, Clinical Science Services Kathleen M. Ziegler, Pharm.D.; Research/Editorial Staff Claudia J. Bonnell, B.S.N., M.L.S.; Kimberly L. Hines, M.S. Blue Cross and Blue Shield Association Medical Advisory Panel Allan M. Korn, M.D., F.A.C.P. Chairman, Senior Vice President, Clinical Affairs/Medical Director, Blue Cross and Blue Shield Association; Alan M. Garber, M.D., Ph.D. Scientific Advisor, Staff Physician, U.S. Department of Veterans Affairs; Henry J. Kaiser, Jr., Professor, and Professor of Medicine, Economics, and Health Research and Policy, Stanford University; Steven N. Goodman, M.D., M.H.S., Ph.D. Scientific Advisor, Professor, Johns Hopkins School of Medicine, Department of Oncology, Division of Biostatistics (joint appointments in Epidemiology, Biostatistics, and Pediatrics). Panel Members Peter C. Albertsen, M.D., Professor, Chief of Urology, and Residency Program Director, University of Connecticut Health Center; Sarah T. Corley, M.D., F.A.C.P., Chief Medical Officer, NexGen Healthcare Information Systems, Inc. American College of Physicians Appointee; Helen Darling, M.A. President, National Business Group on Health; Josef E. Fischer, M.D., F.A.C.S., William V. McDermott Professor of Surgery, Harvard Medical School American College of Surgeons Appointee; I. Craig Henderson, M.D., Adjunct Professor of Medicine, University of California, San Francisco; Jo Carol Hiatt, M.D., M.B.A., F.A.C.S. Chair, Inter-Regional New Technology Committee, Kaiser Permanente; Mark A. Hlatky, M.D., Professor of Health Research and Policy and of Medicine (Cardiovascular Medicine), Stanford University School of Medicine; Saira A. Jan, M.S., Pharm.D., Associate Clinical Professor, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Residency Director and Director of Clinical Programs Pharmacy Management, Horizon Blue Cross and Blue Shield of New Jersey; Leslie Levin, M.B., M.D., F.R.C.P.(Lon), F.R.C.P.C., Head, Medical Advisory Secretariat and Senior Medical, Scientific and Health Technology Advisor, Ministry of Health and Long-Term Care, Ontario, Canada; Bernard Lo, M.D., Professor of Medicine and Director, Program in Medical Ethics, University of California, San Francisco; Randall E. Marcus, M.D. Charles H. Herndon Professor and Chairman, Department of Orthopaedic Surgery, Case Western Reserve University School of Medicine; Barbara J. McNeil, M.D., Ph.D., Ridley Watts Professor and Head of Health Care Policy, Harvard Medical School, Professor of Radiology, Brigham and Women s Hospital; William R. Phillips, M.D., M.P.H., Clinical Professor of Family Medicine, University of Washington American Academy of Family Physicians Appointee; Alan B. Rosenberg, M.D., Vice President, Medical Policy, Technology Assessment and Credentialing Programs, WellPoint, Inc.; Maren T. Scheuner, M.D., M.P.H., F.A.C.M.G., Director, Genomics Strategic Program Area, VA HSR&D Center of Excellence for the Study of Healthcare Provider Behavior, VA Greater Los Angeles Healthcare System; Natural Scientist, RAND Corporation; Adjunct Associate Professor, Department of Health Services, UCLA School of Public Health; J. Sanford Schwartz, M.D., F.A.C.P., Leon Hess Professor of Medicine and Health Management & Economics, School of Medicine and The Wharton School, University of Pennsylvania; Earl P. Steinberg, M.D., M.P.P., President and CEO, Resolution Health, Inc.; Robert T. Wanovich, Pharm.D., Vice-President, Pharmacy Affairs, Highmark, Inc. CONFIDENTIAL: This document contains proprietary information that is intended solely for Blue Cross and Blue Shield Plans and other subscribers to the TEC Program. The contents of this document are not to be provided in any manner to any other parties without the express written consent of the Blue Cross and Blue Shield Association Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 3

4 Assessment Objective Low-level laser therapy refers to the use of red-beam or near-infrared lasers with a wavelength between 600 and 1,000 nm and power from mw. When applied to the skin, these lasers produce no sensation and do not burn the skin. It is hypothesized that the laser light can penetrate deeply beyond the skin where it has therapeutic effects. The exact mechanism of its effects on tissue is unknown: hypotheses have included improved cellular repair and stimulation of the immune, lymphatic, and vascular systems. Low-level laser therapy has been used to treat pain associated with a variety of conditions including soft-tissue injuries, tendinopathies, and osteoarthritis, as well as conditions such as oral mucositis and lymphedema. The purpose of this Assessment is to evaluate the use of lowlevel laser therapy for two conditions: carpal tunnel syndrome and chronic neck pain. Carpal tunnel syndrome was chosen for review because low-level laser devices have received marketing clearance from the U.S. Food and Drug Administration (FDA) specifically for this condition. Chronic neck pain was chosen for review because there is a relatively large body of randomized clinical trials evaluating the use of low-level laser therapy for this condition. It should be instructive to more carefully examine the better studies among these trials to assess the potential effects of this therapy. Background Low-level Laser Therapy Laser radiation is a type of electromagnetic radiation that is uniform in frequency, phase, and polarization. Low-level laser therapy refers to the use of red-beam or near-infrared lasers with a wavelength between 600 and 1,000 nm and power from mw. When applied to the skin, these lasers produce no sensation and do not burn the skin. It is hypothesized that the laser light can penetrate deeply beyond the skin where it has therapeutic effects. The exact mechanism of its effects on tissue is unknown; hypotheses have included improved cellular repair and stimulation of the immune, lymphatic, and vascular systems (Bot and Bouter 2006). Low-level laser therapy in musculoskeletal disorders, according to a definition from the World Association of Laser Therapy, refers to monochromatic light therapy with lasers that have a mean optical output of larger than 1 mw, such as lasers in classes II, IIIa/b and IV. The mechanism by which low-level laser therapy alleviates pain is uncertain, but effects on inflammation, cell proliferation and motility, and collagen synthesis have been proposed. Various treatment regimens have been used in various studies. The World Association of Laser Therapy has published recommendations for dosages for various musculoskeletal conditions (World Association of Laser Therapy 2010). In general, they recommend 4 to 8 joules applied to each trigger point. Most pain regions will have 2 to 3 trigger points. They also suggest daily treatment for 2 weeks or treatment every other day for 3 to 4 weeks. However, there is no rationale or evidence cited for these treatment recommendations. Indications for Low-Level Laser Therapy Other than Those Reviewed in this Assessment. Low-level laser treatment has been evaluated for numerous conditions, including several musculoskeletal conditions such as low back pain, elbow pain, Achilles tendinopathy, jaw pain, shoulder pain, knee pain, and rheumatoid arthritis. A Cochrane review for low-level laser therapy for nonspecific lowback pain concluded that there were insufficient data to draw firm conclusions regarding efficacy, based on a review of 7 randomized clinical trials (Yousefi-Nooraie et al. 2008). A similar conclusion was reached in a Cochrane review of low-level laser for rheumatoid arthritis (Brosseau et al. 2005), but they did find that low-level laser improved pain by 1.1 points on a 10-point visual analog scale relative to placebo. Low-level laser has also been used for wound healing, temporomandibular joint pain, lymphedema, and smoking cessation. The quantity of randomized clinical trials evaluating these other indications appears to be smaller than for the indications reviewed in this Assessment. A few review papers of low-level laser have included a large number of clinical trials, but have combined clinical indications for the purpose of the review, such as treatment of joint disorders and tendinopathies (Bjordal et al. 2003; Tumilty et al. 2010). The number of studies examining a single clinical entity is generally small. FDA Status. A large number of low-level lasers have received clearance for marketing from the FDA through the 510(k) approval process. The Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

5 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain products have all been classified by the code of federal regulations as 21 CFR infrared lamp, which according to the code is an infrared lamp is a device intended for medical purposes that emits energy at infrared frequencies (approximately 700 nanometers to 50,000 nanometers) to provide topical heating. Many products also approved in this category are not laser devices, and are intended specifically to generate topical heating. However, many of the approval documents for specific products characterize their device as a nonheating infrared lamp and refer to CFR as defining a nonheating lamp. This type of lamp is considered a class II device, which is subject to a much lower level of regulation than medical lasers, which emit light in the visible light spectrum. Different products have various indications associated with their approval, including carpal tunnel syndrome, pain associated with knee disorders, and minor chronic pain. It appears that treatment of pain is the only application for which the various products have gained approval. Carpal Tunnel Syndrome Carpal tunnel syndrome is caused by compression of the median nerve by surrounding structures in the wrist, resulting in pain, tingling and weakness in the muscles of the hand (Shapiro and Preston 2009). The syndrome is often caused by frequent repetitive action of the wrist often associated with specific occupations. The diagnosis can be made based on clinical signs and symptoms. Electrodiagnostic testing is considered the gold standard. Various measures of nerve conduction velocity, distal latency, and potential amplitude are often abnormal in carpal tunnel syndrome (Shapiro and Preston 2009). Conservative treatment consists of nonsteroidal anti-inflammatory drugs, limitation of activities that provoke symptoms, and wrist splinting (Shapiro and Preston 2009). Other treatments include oral corticosteroids, local corticosteroid injections, or ultrasound therapy. If conservative therapy fails, surgical treatment of carpal tunnel syndrome is usually recommended and has good success rates. In a randomized trial of surgery versus corticosteroid injection, patients undergoing surgery had a mean 24-point improvement in a 50-point symptom scale versus 8 points for patients having corticosteroid injection (Hui et al. 2005). Chronic Neck Pain Neck pain can have many etiologies (Devereaux 2009). However, with regard to low-level laser therapy, the type of pain disorder included in trials was either described as myofascial pain syndrome or undifferentiated chronic neck pain in the absence of neurological signs and symptoms or known cervical, rheumatologic, or systemic disease. Myofascial pain syndrome is characterized by pain originating from trigger points located in taut bands in skeletal muscle. Trigger points are small areas of the muscle that cause radiating pain upon palpation. The neck and upper back are the most commonly affected areas in myofascial pain syndrome because of the involvement of the trapezius muscle in most cases (Borg-Stein and Simons 2002). Some authors believe that myofascial pain syndrome is a localized variant of fibromyalgia (Borg- Stein and Simons 2002). Treatment for myofascial pain syndrome has usually been symptomatic. Cold and heat application, massage, local anesthetics, and needle injections are among the methods used for treatment. The efficacy of these various treatments is difficult to assess, and no treatment modality appears to be considered the standard of care. A Cochrane review by Kroeling et al. (2009) assessed the evidence on various forms of electrotherapy such as repetitive magnetic stimulation and transcutaneous electrical nerve stimulation. The studies were all characterized as low-quality evidence, and thus the authors made no definitive statements regarding efficacy of any modality. Similarly, in a Cochrane review by Gross et al. (2010) on manipulation or mobilization for neck pain, the studies were mostly characterized as low-quality evidence. The central conclusion was that manipulation and mobilization are similar in effect. A Cochrane review of massage for mechanical neck disorders (Haraldsson et al. 2006) declined to make recommendations regarding this treatment because the evidence did not allow any conclusion regarding efficacy. The applicability of the studies in these reviews to this topic may be limited by differences in patient selection and disease, as these reviews were generally not restricted to the indication of myofascial pain syndrome Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 5

6 Outcomes Measured for Selected Conditions For pain-related conditions, a visual analog scale (VAS) is almost universally assessed as an outcome measure in clinical trials. For carpal tunnel syndrome, Levine et al. (1993) developed an 11-item questionnaire assessing symptom severity, which has been used as an outcome measure in many clinical trials of carpal tunnel syndrome. Each item is rated on a 5-point scale. Ozyurekoglu et al. (2006) estimated that the minimum clinically important difference in this scale is about 1 point. Katz et al. (1994) showed that measures of symptom severity as assessed by the symptom severity score were more sensitive indicators of treatment response than test performance measures such as grip and pinch strength. Levine et al. (1993) also developed an 8-item questionnaire assessing functional status. Electrophysiologic studies have also been used as secondary outcome measures in carpal tunnel syndrome. However, the correlation between symptoms and such studies may not be high. Chan et al. (2007) reported no correlation between electrophysiologic studies and symptom severity in carpal tunnel syndrome patients. However, they are less subject to reporting bias than self-reported symptom measures. For neck pain, in addition to the VAS, various neck pain scales have been developed. In the studies by Chow et al. included in this Assessment (2004; 2006), the Northwick Park Neck Pain Questionnaire was used. This is a 9-question instrument with 5 guided answers to each question indicating greater or lesser severity of neck pain severity and functional disability (Leak et al. 1994). Sim et al. (2006) estimated that a 25% reduction from baseline was the minimum clinically important difference for this scale. Other outcome measures used in studies of low-level laser therapy for neck pain include the McGill Pain Questionnaire and the Neck Pain and Disability Scale. The McGill Pain Questionnaire is used to measure pain of any kind. In addition to measuring severity of pain, it can be used to describe the symptoms and character of the pain. The multiplicity of measures used in studies assessing therapies in which pain relief is the principal outcome makes it difficult to compare outcomes between studies. However, it might be reasonable to assume that approximately a 25% to 30% change from baseline in a pain scale constitutes a clinically important response for musculoskeletal conditions. In a study enrolling subjects with several different kinds of musculoskeletal conditions, Salaffi et al. (2004) found that a percentage change of 33% from baseline on a numerical rating score was the best estimate of a much better improvement. Ostelo et al. (2008) in their review and consensus workshop on back pain concluded that a 30% change from baseline constituted a useful threshold for a clinically meaningful improvement. Methods Search Methods Searches of the MEDLINE database (via PubMed) using the terms laser or low-level laser, carpal tunnel, neck pain, myofascial pain were carried out in May References from recent review articles and meta-analyses were examined. References were limited to English-language articles in human subjects. Study Selection There were a large number of studies evaluating low-level laser for the treatment of carpal tunnel syndrome or neck pain. Thus, it was decided to select for presentation the subset of rigorously done studies that evaluated clinically relevant outcomes. Also, the clinically relevant outcomes had to exhibit some durability beyond the acute period of treatment. Thus, studies had to meet the following criteria: n published in a peer-reviewed journal n randomized, sham-controlled clinical trial (if adjunctive therapies were used, then they should be applied to both groups) n outcomes measured at least 2 weeks beyond the end of the treatment period n for neck pain studies, patients included need to have chronic pain These selection criteria resulted in the exclusion of many studies that have been included in other reviews of low-level laser therapy. For example, a meta-analysis by Chow et al. (2009) identified 16 randomized trials of low-level laser therapy for management of neck pain. Several of the studies included in that metaanalysis were excluded from detailed review in this Assessment because some studies evaluated acute neck pain, some had insufficient follow-up beyond the period of treatment, one Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

7 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain had no sham control, and some were foreignlanguage publications. For carpal tunnel syndrome, these selection criteria resulted in the exclusion of studies that have been cited in other reviews (e.g., Naeser 2006). An early study sponsored by and carried out in a General Motors factory has never been published in a peer-reviewed journal (available online at html). A study used in support of FDA 510(k) marketing clearance also has never been fully published. Medical Advisory Panel Review This Assessment was reviewed by the Blue Cross and Blue Shield Association Medical Advisory Panel (MAP) on June 30, In order to maintain the timeliness of the scientific information in this Assessment, literature searches were performed subsequent to the Panel s review (see Search Methods ). If the search updates identified any additional studies that met the criteria for detailed review, the results of these studies were included in the tables and text where appropriate. There were no studies that would change the conclusions of this Assessment. Formulation of the Assessment Patient Indications Carpal tunnel syndrome. Studies evaluating low-level laser therapy as a treatment for carpal tunnel syndrome have generally included patients diagnosed with the syndrome using standard clinical means, but without complicating comorbidities and without prior surgery. Neck pain. Studies evaluating low-level laser as a treatment for neck pain have generally included patients diagnosed with myofascial pain syndrome or with undifferentiated chronic neck pain without evidence of neurologic or spinal disorder. Technologies to be Compared Clinical trials have been performed comparing low-level laser to a sham placebo and compared to some other active treatments. However, the trials comparing low-level laser to active treatments were flawed by a lack of blinding and lack of sham placebo and thus did not meet selection criteria for this Assessment. In addition, the alternative treatments in these trials are of uncertain efficacy, as there were no untreated groups in these studies. Thus the sham-controlled clinical trials can only assess the efficacy of low-level laser treatment either by itself or as an adjunct to another treatment (if the sham group also receives this adjunct treatment). The comparative efficacy of low-level laser therapy versus an alternative treatment cannot be assessed with the current evidence. For most alternative treatments such as splinting (for carpal tunnel syndrome) and stretching exercises (for neck pain), low-level laser treatment can be administered in addition to these treatments. Thus, it is reasonable to evaluate whether low-level laser improves outcomes in addition to these treatments. However, according to the World Association of Laser Therapy, corticosteroid treatment is incompatible with low-level laser treatment. The relative efficacy of a treatment that must be administered instead of low level laser treatment is critical to know, whereas the relative efficacy of a treatment that can be given as an adjunct to low-level laser may be less important to know. Health Outcomes For both indications reviewed in this Assessment, the principal outcome is relief of pain. Outcomes should be measured with a validated outcome measure and should be consistent with a clinically relevant amount of pain relief. The improvement should persist beyond the period of treatment for some amount of time. For carpal tunnel syndrome, changes in EMG results might provide supportive evidence of efficacy, but would be insufficient by themselves to demonstrate an important health outcome. Low-level laser treatment has not been associated with any adverse effects. The laser is painless and cannot be felt during treatment. Assessment Questions 1. What is the effect of low-level laser therapy on carpal tunnel syndrome? 2. What is the effect of low-level laser therapy on chronic neck pain? Review of Evidence Carpal Tunnel Syndrome Four randomized, clinical trials (Ekim et al. 2007; Evick et al. 2007; Chang et al. 2008; Irvine et al. 2004) enrolling a total of 151 patients met the inclusion criteria (Table 1 and 2). Two of the studies enrolled fewer than 20 patients (Ekim et al. 2007; Irvine et al. 2004), and the largest study enrolled 81 patients (Evick et al Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 7

8 Table 1. Characteristics of Randomized Clinical Trials of Laser Therapy for Carpal Tunnel Syndrome Study/Year Patients Treatment regimen Co-interventions Outcome measures Length of follow-up Ekim et al Rheumatoid arthritis patients with carpal tunnel syndrome 780 nm laser 7.5 joules per treatment 10 treatments over 2 weeks No analgesics allowed DMARDs continued Pain VAS Symptom Severity Scale Functional Status Scale Grip Strength EMG studies 2.5 months after end of treatment Evcik et al Patients with carpal tunnel syndrome 830 nm laser 14 joules per treatment 10 treatments over 2 weeks No AIDS or other treatment Wrist splint at night Pain VAS (day and night) Symptom Severity Scale Functional Status Scale Hand grip strength Pinch grip strength EMG studies 4 weeks and 12 weeks after end of treatment Chang et al Patients with carpal tunnel syndrome 830 nm laser 9.7 joules per treatment 10 treatments over 2 weeks No medications or other treatments allowed Pain VAS Symptom Severity Scale Functional Status Scale Grip Strength EMG studies 2 weeks after end of treatment Irvine et al Patients with carpal tunnel syndrome, excluded if evidence of axonal loss 860 nm laser 6 joules per treatment 15 treatments over 5 weeks No medications or other treatments allowed Symptom Severity Scale Functional Status Scale Purdue pegboard test EMG studies 4 weeks after end of treatment Abbreviations: DMARDs: disease-modifying antirheumatic drugs; EMG: electromyelogram; AIDs: nonsteroidal anti-inflammatory drugs; VAS: visual analog scale; Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

9 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Table 2. Selected Outcomes of Controlled Trials of Laser Therapy for Carpal Tunnel Syndrome Author/Year N Outcome measure, assessment time Results Between-group p value Ekim et al laser 9 sham 3 months post-treatment Pain VAS Baseline 3 months Adjust Diff Significant Laser Sham Symptom Severity Scale Baseline 3 months Adjust Diff Laser Sham Functional Status Scale Baseline 3 months Adjust Diff Significant Laser Sham Grip Strength, Motor Distal Latency, Motor Nerve Conduction Velocity, Sensory Distal Latency, Palm-wrist nerve conduction velocity, % Tinel positive, % Phalen positive Not abstracted, reported in manuscript All Evcik et al laser 40 sham 12 weeks post-treatment Pain VAS (day) Baseline 12 weeks Laser Sham Pain VAS (night) Baseline 12 weeks Laser Sham Symptom severity score Baseline 12 weeks Laser Sham No between group p values reported in tables, described in text as no significant differences between groups Hand grip strength Baseline 12 weeks Laser Sham Pinch grip strength Baseline 12 weeks Laser Sham Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 9

10 Table 2. Selected Outcomes of Controlled Trials of Laser Therapy for Carpal Tunnel Syndrome (cont d) Author/Year N Outcome measure, assessment time Results Between-group p value Chang et al laser 20 sham 36 patients, 4 with bilateral carpal tunnel 2 weeks post-treatment Pain VAS Baseline (median) 2 weeks (median) <0.05 Laser 6 0 Sham 6 6 Symptom Severity Scale Baseline (median) 2 weeks (median) <0.05 Laser Sham Functional Status Scale Baseline (median) 2 weeks (median) <0.05 Laser Sham Irvine et al laser 8 sham 4 weeks post-treatment Symptom Severity Scale Baseline 4 weeks Laser Sham Functional disability scale Baseline 4 weeks Laser Sham Purdue pegboard, EMG studies Not abstracted All Abbreviations: EMG: electromyelogram; : not significant; VAS: visual analog scale Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

11 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain 2007). All the studies used a treatment schedule of 5 treatments per week; 3 of them for a total of 2 weeks. The laser wavelength and total energy applied varied between the studies. Two of the 4 studies come from investigators in Turkey and one from Taiwan. In terms of the quality of the studies, all of the reports described the trials as double-blind, where the investigators were not aware of the treatment being given, and post-treatment assessments were performed by someone not aware of the treatment being given. All studies had explicit statements regarding co-interventions allowed during treatment. The study by Evcik et al. (2007) had all subjects use a wrist splint at night. The study by Ekim et al. (2007) had patients continue their disease-modifying antirheumatic drugs. Otherwise, in all the studies, no other treatments or pain medications were allowed. The study by Chang et al. (2008) is problematic in terms of the independence of the measurements. Thirty-six patients were enrolled, but in 4 of the patients, both hands were evaluated in the study. It is not stated anywhere how patients with bilateral disease were randomized in the study, and no description of any statistical procedures done to account for this issue is noted. The largest study is from Evcik et al. (2007). In this study, 81 patients were randomized to either low-level laser or sham laser. Patients with bilateral disease were included in this study, but it is clear that patients, not hands, were randomized and analyzed. Patients were not allowed to use nonsteroidal anti-inflammatory drugs and were given a wrist splint to use at night. For the principal outcomes of the VAS pain scale assessed for daytime and nighttime and the Levine symptom severity score, there were no statistically significant differences at 4 weeks or 12 weeks follow-up between groups. Both groups had improvements over time. Some improvements were noted in the lasertreated group for hand grip, pinch grip, and some EMG measurements, but appropriate between-group statistical tests were not provided in the paper. In the study by Chang et al. (2008), 40 wrists in 36 patients were randomized to low-level laser or sham laser. As noted previously, it is not noted how the patients with bilateral disease were randomized or analyzed; it appears as though they were analyzed as independent observations. Follow-up extended 2 weeks beyond the 2-week period of treatment. In this study, patients treated with low-level laser had dramatic improvements compared to virtually no change in sham-treated patients. The VAS pain scores changed from 6 to zero, the symptom severity scores from 30.1 to 19.4, and the functional status score from 18.7 to 20.0, all statistically significant compared to minimal changes in the sham-treated patients. There were also statistically significant differences in favor of the laser-treated group for grip strength, lateral prehension, and digital prehension. The study by Ekim et al. (2007) randomized patients with rheumatoid arthritis and carpal tunnel syndrome to low-level laser or sham laser. The study enrolled only 19 total patients. Follow up was at 3 months after the end of treatment. The study showed statistically significant differences in improvement in the lasertreated group compared to the sham-treated group for the VAS pain score and the functional status scale at 3 months. The symptom severity scale and all other measures including EMG outcomes were not statistically significant at 3 months. The mean difference between groups for the VAS pain score was 10 points on a 100 point scale, with baseline value of 56. The study by Irvine et al. (2004) randomized 15 patients and followed outcomes out to 4 weeks beyond the 5-week treatment period. In terms of the primary outcome of the symptom severity score, both groups improved over time with no significant difference between groups. No other outcomes differed between groups. Discussion. In sum, there is not a very strong evidence base of rigorous studies evaluating the use of low-level laser for treatment of carpal tunnel syndrome. Two of the clinical trials were extremely small, one of which evaluated carpal tunnel syndrome only in patients with rheumatoid arthritis. In the 2 larger studies (Evcik et al. 2007; Chang et al. 2008), the results are not consistent; one study showed improvement over time in both groups with no difference between treatments, and the other showed a dramatic improvement only in the laser-treated group. No study stands out beyond the others as so methodologically strong that its results should be considered conclusive. In comparing the patient characteristics, trial design, and treatment parameters, there does not appear to be great differences between the two trials. The trial by Chang et al. (2008) 2010 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 11

12 specified that patients should have had initial onset of carpal tunnel syndrome at least 1 year prior to the trial, whereas there was no information on disease onset in the trial of Evcik et al. (2007). The trial by Evcik et al. (2007) also included a co-intervention of a wrist splint, which was specifically not allowed in the study of Chang et al. (2008). Other issues concerning the study of Chang et al. (2008) is the relatively short follow-up time beyond treatment of only 2 weeks, and the uncertain issues regarding the randomization and analysis of patients with bilateral disease. In sum, there is insufficient evidence regarding the effectiveness of low-level laser for carpal tunnel syndrome. Chronic Neck Pain Six clinical trials enrolling a total of 285 patients met the inclusion criteria (Chow et al. 2004, 2006; Altan et al. 2005; Gur et al. 2004; Ilbuldu et al. 2004; Ceccherelli et al. 1989). Descriptive characteristics of the trials are shown in Table 3 and results in Table 4. The studies by Chow et al. enrolled patients with undifferentiated chronic neck pain. All the other studies enrolled patients meeting their criteria for myofascial pain. All studies excluded patients with neurologic symptoms and comorbid diseases. One study enrolled as few as 20 patients, and the largest study enrolled 90 patients. Patients received a total of between 10 and 14 treatments; treatment periods varied between 2 and 7 weeks. The laser wavelength and total energy applied per treatment varied between the studies. Several of the papers did not report the energy applied per treatment or per point, and such values were estimated in a meta-analysis by Chow et al. (2009). According to treatment parameters recommended by the World Association of Laser Therapy, only the studies by Chow et al. (2004, 2006) applied the minimum recommended 4 joules per point, but as noted previously, the rationale supporting the minimum recommended doses is not provided. Regarding the quality of the studies, the studies were evaluated by the Jadad score in the metaanalysis by Chow et al. (2009). The Jadad score evaluates randomization, blinding, and withdrawals and dropouts, and 3 is considered a reasonable score. Only the study by Ilbuldu et al. had a score below 3. Regarding possible cointerventions during the study, some studies did not thoroughly describe. Table 3 shows the variations among the studies: some did not mention the use of pain medications, some studies did not allow other treatments, while other studies gave instructions or required exercise and stretching during the period of treatment. In the largest study by Chow et al. (2006), 90 patients with chronic neck pain were randomized to low-level laser treatment or sham laser. Patients were allowed to maintain their usual pain medications, but no other treatments were allowed. At 5 weeks after the 7-week treatment period, laser-treated patients reported an improvement in VAS pain scale of 2.7 points compared to baseline, versus a 0.3 point worsening for sham-treated patients. Consistent and statistically significant findings were noted for the neck pain questionnaire scores and neck pain disability scores. A mean average percent improvement was calculated from a question asking patients to estimate how much better they felt in percentage units. The laser-treated group reported a mean percent improvement of 43.8% and the sham-treated group a mean percent improvement of 2.1%. The study appears to be well conducted. One point of concern is although the randomization procedure appears reasonably done, the baseline VAS pain scores of the treatment groups were significantly different, as the laser-treated group reported much greater pain than the sham group (5.9 versus 4.0). Such a difference might bias favorable results in the laser group by regression to the mean. The authors describe in the discussion a regression analysis, which they state refutes this objection, and also raise the issue of the other measures of outcome. However, baseline values of the other outcome measures were not shown, so possible imbalances in these other measures cannot be evaluated. The study by Altan et al. (2005) randomized 48 patients with myofascial pain syndrome to laser or sham. In addition to laser or sham, patients were instructed to perform daily isometric exercises and stretching just short of pain. For the principal outcome of the pain VAS, both laser and sham groups had improved scores at 12 weeks after treatment, and no significant differences between treatment groups. None of the other outcomes including assessments of tenderness, trigger points, and neck flexion showed differences in outcomes between groups Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

13 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Table 3. Characteristics of Randomized Clinical Trials of Laser Therapy for Neck Pain Author Patients Treatment regimen Co-interventions Outcome measures Length of follow-up Chow et al n Unilateral or bilateral neck pain greater than 3 months, no abnormal neurologic findings n Recruited from newspaper ads n 830 nm laser n Maximum 30 min. session n 14 treatments over 7 weeks n 9 joules per point* n Maintain usual pain meds, no other treatments allowed n Pain VAS n SF-36 physical n SF-36 mental n Neck Pain Questionnaire n Neck Pain Disability n McGill Pain Questionnaire n Self-Assessed Improvement 5 weeks after end of treatment Altan et al n Myofascial pain syndrome greater than 3 months, no abnormal anatomy n 904 nm laser n No pain meds allowed n 10 treatments over 2 weeks n Instructed to perform n 0.5 joules per point* exercises, stretching n Pain VAS 12 weeks after end n Pain- 5 point scale of treatment n Tenderness measures Chow et al n Unilateral or bilateral neck pain, no abnormal neurologic findings n 830 nm laser n Maximum 30 min. session n 14 treatments over 7 weeks n 9 joules per point* n Maintain usual pain meds, no other treatment mentioned n Pain VAS n SF-36 physical n SF-36 mental n Neck Pain Questionnaire n McGill Pain Questionnaire n VAS for self-improvement 5 weeks after end of treatment Gur et al n Myofascial pain syndrome greater than 1 year, no neurologic deficits n 904 nm laser n 3 minutes per trigger pt n 10 treatments over 2 weeks n joules per point* n Other meds not mentioned n General posture and ergonomic advice given n Pain VAS at rest n Pain VAS at movement n Neck Pain Disability n Nottingham Health Profile n Beck Depression Inventory 10 weeks after end of treatment * Not reported in study; estimated by Chow et al. (2009) meta-analysis 2010 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 13

14 Table 3. Characteristics of Randomized Clinical Trials of Laser Therapy for Neck Pain (cont d) Author Patients Treatment regimen Co-interventions Outcome measures Length of follow-up Ilbuldu et al n Women only with myofascial pain syndrome, several comorbidities excluded n 632 nm laser n 12 treatments over 3 weeks n 2 joules per trigger point n dry needling control group in addition to sham control group n Other meds not mentioned n Exercise and stretching required during treatment n Pain VAS at rest 6 months after end n Pain VAS at activity of treatment n Pain threshold n Pain tolerance n Analgesic use n Cervical range of motion Ceccherelli et al n Women with myofascial pain syndrome without neurological deficits n 904 nm laser n Not mentioned n VAS pain 3 months after end n 12 treatments over 4 weeks n McGill Pain Questionnaire of treatment n 1 joule per tender point Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

15 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Table 4. Selected Outcomes of Controlled Trials of Laser Therapy for Chronic Neck Pain Author N Outcome measure, assessment time Results Between-group p value Chow et al laser 45 sham 5 weeks post-treatment VAS 5 week baseline difference laser-sham diff <0.001 Laser ** Sham 0.3 SF-36 physical 5 week baseline difference laser-sham diff <0.02 Laser Sham -1.3 SF-36 mental 5 week baseline difference laser-sham diff Laser Sham 5.4 Neck Pain questionnaire 5 week baseline difference laser-sham diff <0.005 Laser Sham -0.6 Neck Pain disability 5 week baseline difference laser-sham diff <0.001 Laser Sham -3.1 % Self-assessed improvement 5 week baseline difference laser-sham diff <0.001 Laser 43.8% 41.7% Sham 2.1% Altan et al laser 25 sham 12 weeks post-treatment Pain VAS Baseline 12 weeks Laser Sham Pain (5 point scale) Baseline 12 weeks Laser Sham Tenderness (0 18 pt) Baseline 12 weeks Laser Sham Trigger points (kg/cm2) Baseline 12 weeks Laser Sham All other measures Not abstracted 2010 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 15

16 Table 4. Selected Outcomes of Controlled Trials of Laser Therapy for Chronic Neck Pain (cont d) Author N Outcome measure, assessment time Results Chow et al laser 10 sham 5 weeks post treatment VAS 5 week baseline difference laser-sham diff Laser Sham -0.7 SF-36 physical Laser Sham 1.2 SF-36 mental Laser Sham 0.0 Neck Pain questionnaire Laser Sham McGill Pain Score total Laser Sham 1.1 % Self-assessed improvement Laser 66.7% 50.1% Sham 16.6% Gur et al laser 30 sham 10 weeks post treatment Pain VAS at rest Baseline 10 weeks Laser Sham Pain VAS at movement Laser Sham Neck Pain disability scale Laser Sham Nottingham Health Profile Laser Sham Beck Depression Inventory Laser Sham # of trigger points Laser Sham * only final values compared between groups for the statistical test performed ** baseline values were statistically significant between laser and control groups, laser 1.9 pts greater baseline pain than control. Between-group p value <0.001 * * <0.01* * * <0.01* Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

17 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain Table 4. Selected Outcomes of Controlled Trials of Laser Therapy for Chronic Neck Pain (cont d) Author N Outcome measure, assessment time Results Between-group p value Ilbuldu et al laser 20 sham (20 dry needle not abstracted) 6 months post treatment Pain VAS at rest Baseline 6 months Laser Sham Pain VAS at activity Laser Sham Pain threshold Laser Sham Pain tolerance Laser Sham Analgesic use Laser Sham Various cervical range of motion measurements and functional status Not abstracted All Ceccherelli et al laser 14 sham 3 months post treatment VAS Final value Laser 8.5 <0.001* Sham 35.6 * only final values compared between groups for the statistical test performed 2010 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 17

18 Chow et al. (2004) randomized 20 patients with chronic neck pain to low-level laser treatment or sham laser. The study appears to be a pilot version of the 2006 study by the same group reviewed in this Assessment (Chow et al. 2006), as the treatment regimen and laser parameters are identical to that study. At 5 weeks after a 7-week treatment period, some, but not all, of the outcomes were consistent with improvement in the laser-treated patients. Although the outcome of a difference in VAS pain score was not statistically significant, the percent change in VAS pain score was statistically significant, as was a change in the neck pain questionnaire scores, McGill pain questionnaire, and a global measure of self-reported improvement. The VAS pain scores improved 2.1 points in the lasertreated group and 0.7 in the sham-treated group. In the study by Gur et al. (2004), 30 patients each were randomized to laser or sham treatment. Treatment was applied for 2 weeks, and the final outcomes were assessed 10 weeks after the final treatment. In the presentation of the results, the authors cite numerous outcomes in which the improvement was statistically significant in the laser-treated group but not in the sham-treated groups. This would be suggestive of a treatment benefit, but is not the appropriate analysis. The other presentation of results compares the final values of the outcomes, which is one way to present results, but may be an underpowered analysis, because it does not take into account the baseline values. Using this method, the authors found a significant difference in favor of laser treatment for the neck pain disability score and the number of trigger points. The VAS pain-at-rest, VAS pain at movement, Nottingham Health Profile, and Beck Depression Inventory were not significantly different at 10 weeks. However, the magnitude of the changes in pain scores was greater in the laser-treated group than the sham-treated group (i.e., VAS pain at rest, 3.2 versus 0.6) and the other outcomes also favored the laser-treated group. In the study by Ilbuldu et al. (2004), 40 women with myofascial pain syndrome were randomized to laser (n=20) or sham laser (n=20). Another study arm of 20 women also received dry needling; however, those outcomes are not considered in this Assessment. The laser device used in this trial used a wavelength of nm, which is in the visible light spectrum, rather than the infrared spectrum. Details of the blinding are not provided in the report. Patients were also instructed to perform muscle stretching exercises during the treatment period. At a 6-month time point of assessment, there were no significant differences between groups for any outcome measured. Both groups had improvements over the time period. For example the VAS at rest improved from 5.5 to 2.2 for the laser-treated group, and from 5.7 to 2.9 for the sham-treated group. In the study by Ceccherelli et al. (1989), 13 and 14 women with myofascial pain syndrome were treated with laser and sham laser, respectively. No mention is made of co-interventions in this study. Only the VAS pain scale was assessed at 3 months after treatment. At this time point, the laser-treated group had a mean pain score of 8.5 and the sham-treated group had a mean score of 35.6 (p<0.001). Baseline values were not taken into account in this comparison. However, the McGill pain scores were similar at baseline between the groups. A possible concern in this study is some imbalance in the groups; a complete description of the characteristics of the patients is not given, but the groups had a 6-year difference in mean age (laser group mean age 43.7 years, sham group mean age 49.6 years). The previously described studies were all included in a meta-analysis by Chow et al. (2009) and summarized in a group of studies that calculated a summary mean difference in VAS pain scale. The findings reported in the meta-analysis cannot be directly compared to the smaller set of studies reported here. Chow et al. (2009) reported an overall summary estimate of a difference of 19.9 points (on a 100-point VAS scale) between laser and sham groups. This summary estimate includes foreign-language publications and studies without follow-up beyond treatment. It only summarizes the earliest reported outcome data, and includes at least one study with no sham control. Chow et al. (2009) also report a summary estimate of a difference of 22 points among a set of studies that reported follow-up data between 1 and 22 weeks after the end of treatment. All of the studies except those of Chow et al. (2004, 2006) are included in this particular analysis. This analysis appears to have potential analytic problems biasing the results towards showing the effectiveness of laser therapy. The study by Gur et al. (2004) is double-counted, one time at each follow-up point. It includes a study by Hakguder et al. (2003), which has no sham Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

19 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain control. Finally, the study by Ceccherelli et al. (1989) contributes a highly improbable value of 44.8 points difference in VAS to the analysis. The baseline VAS pain value in the laser-treated group in that study was more than 17 points worse than the sham-treated group. This difference in pain disappeared in early assessments of pain during treatment, indicative of some problem with the baseline measurement. These problematic studies contributed mean differences of 35.9, 26.4, and 44.8 in the VAS scale to the analysis comprising about 40% of the weight of the summary estimate. Thus, it is likely that the summary estimate of 22 points is biased towards an exaggeration of the benefit associated with laser therapy. In addition, analysis of heterogeneity of the included trials showed statistically significant heterogeneity (p<0.0001, I2 = 86.6%). It should be noted that the trials of Chow et al. (2004, 2006) were not included in the meta-analytic estimate of follow-up data, apparently because the 5-week post-treatment outcome assessment was the initial outcome assessment, rather than a follow-up assessment from those trials. Discussion In sum, the clinical trials of laser therapy for chronic neck pain have inconsistent results. Two of the studies (Chow et al. 2006; Ceccherelli et al. 1989) could be considered positive studies. Overall, the studies are characterized by small sample sizes, limited statistical power, and limited long-term follow-up. A difference in the findings appears to be in the outcomes of the control group, as the laser-treated group in all studies improves. However, in the studies by Altan et al. (2005) and Ilbuldu et al. (2004), the sham-treated groups all experienced improvement similar to the laser-treated groups, thus, producing a negative clinical trial. In all the other studies, the sham-treated groups did not improve at all or improved minimally compared to the lasertreated groups. Two of these 4 studies did not all show statistically significant findings for the principal outcome, but one had very weak statistical power due to small sample size (Chow et al. 2004) and another may have used suboptimal statistical analysis (Gur et al. 2004). The number of studies is too small to examine whether differences in patient selection, treatment regimen, or co-interventions are associated with outcome difference. The dosage, in terms of joules applied to each trigger point during each session, varied from 0.18 to 9 joules. The 2 negative studies both instructed and required patients to perform stretching and exercises, which may account for the improvement in the sham-treated groups in those studies. Summary of Application of the Technology Evaluation Criteria Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether low-level laser therapy for the treatment of carpal tunnel syndrome or chronic neck pain meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate governmental regulatory bodies. Several low-level laser devices have received 510(k) marketing clearance from the U.S. Food and Drug Administration for the clinical indication of carpal tunnel syndrome. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. For the clinical indication of carpal tunnel syndrome, the existing randomized clinical trials are insufficient to make conclusions regarding the effect of low-level laser therapy. The findings of the 4 studies are inconsistent. No one study is so methodologically sound that its results would be definitive. In general, the studies were small and most studies did not follow patients for long periods of time beyond treatment. For the clinical indication of chronic neck pain, the existing randomized clinical trials are insufficient to make conclusions regarding the effect of low-level laser therapy. The findings of the 6 studies are variable. Again, no one study is so methodologically sound that its results would be definitive. In general, the studies were small and most studies did not follow patients for long periods of time beyond treatment Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 19

20 3. The technology must improve the net health outcome; and 4. The technology must be as beneficial as any established alternatives. The evidence is insufficient to make conclusions regarding whether low-level laser therapy either improves the net health outcome or is as beneficial as any established alternatives for the indications of carpal tunnel syndrome or chronic neck pain. 5. The improvement must be attainable outside the investigational settings. It has not yet been demonstrated whether lowlevel laser therapy improves health outcomes in the investigational setting. Therefore, it cannot be demonstrated whether improvement is attainable outside the investigational settings. For the above reasons, low-level laser therapy for carpal tunnel syndrome or for chronic neck pain does not meet the TEC criteria Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

21 Low-Level Laser Therapy for Carpal Tunnel Syndrome and Chronic Neck Pain References Altan L, Bingol U, Aykac M et al. (2005). Investigation of the effect of GaAs laser therapy on cervical myofascial pain syndrome. Rheumatol Int, 25:23-7. Bjordal JM, Couppe C, Chow RT et al. (2003). A systematic review of low level laser therapy with location-specific doses for pain from joint disorders. Aust J Physiother, 49(2): Borg-Stein J, Simons DG. (2002). Focused review: myofascial pain. Arch Phys Med Rehabil, 83(3 Suppl 1):S40-7, S48-9. Bot SD, Bouter LM. (2006). The efficacy of low level laser for chronic neck pain. Pain, 124(1-2):5-6. Brosseau L, Robinson V, Wells G et al. (2005). Low level laser therapy (Classes I, II and III) for treating rheumatoid arthritis. Cochrane Database Syst Rev, (4):CD Ceccherelli F, Altafini L, Lo Castro G et al. (1989). Diode laser in cervical myofascial pain: a double-blind study versus placebo. Clin J Pain, 5: Chan L, Turner JA, Comstock BA et al. (2007). The relationship between electrodiagnostic findings and patient symptoms and function in carpal tunnel syndrome. Arch Phys Med Rehabil, 88(1): Chang WD, Wu JH, Jiang JA et al. (2008). Carpal tunnel syndrome treated with a diode laser: a controlled treatment of the transverse carpal ligament. Photomed Laser Surg, 26: Chow RT, Barnsley L, Heller GZ et al. (2004). A pilot study of low-power laser therapy in the management of chronic neck pain. J Musculoskeletal Pain, 12: Chow RT, Heller GZ, Barnsley L. (2006). The effect of 300 mw, 830 nm laser on chronic neck pain: a doubleblind, randomized, placebo-controlled study. Pain, 124: Chow RT, Johnson MI, Lopes-Martins RA et al. (2009). Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet, 374: Devereaux M. (2009). Neck pain. Med Clin North Am, 93(2):273-84, vii. Ekim A, Armagan O, Tascioglu F et al. (2007). Effect of low level laser therapy in rheumatoid arthritis patients with carpal tunnel syndrome. Swiss Med Wkly, 137: Evcik D, Kavuncu V, Cakir T et al. (2007). Laser therapy in the treatment of carpal tunnel syndrome: a randomized controlled trial. Photomed Laser Surg, 25:34-9. Gross A, Miller J, D Sylva J et al. (2010). Manipulation or mobilisation for neck pain. Cochrane Database Syst Rev, (1):CD Gur A, Sarac AJ, Cevik R et al. (2004). Efficacy of 904 nm gallium arsenide low level laser therapy in the management of chronic myofascial pain in the neck: a double-blind and randomize-controlled trial. Lasers Surg Med, 35: Hakguder A, Birtane M, Gurcan S et al. (2003). Efficacy of low level laser therapy in myofascial pain syndrome: an algometric and thermographic evaluation. Lasers Surg Med, 33(5): Haraldsson BG, Gross AR, Myers CD et al.; Cervical Overview Group. (2006). Massage for mechanical neck disorders. Cochrane Database Syst Rev, (3):CD Hui AC, Wong S, Leung CH et al. (2005). A randomized controlled trial of surgery vs steroid injection for carpal tunnel syndrome. Neurology, 64(12): Ilbuldu E, Cakmak A, Disci R et al. (2004). Comparison of laser, dry needling, and placebo laser treatments in myofascial pain syndrome. Photomed Laser Surg, 22: Irvine J, Chong SL, Amirjani N et al. (2004). Doubleblind randomized controlled trial of low-level laser therapy in carpal tunnel syndrome. Muscle Nerve, 30: Katz JN, Gelberman RH, Wright EA et al. (1994). Responsiveness of self-reported and objective measures of disease severity in carpal tunnel syndrome. Med Care, 32(11): Kroeling P, Gross A, Goldsmith CH, et al. (2009). Electrotherapy for neck pain. Cochrane Database Syst Rev, (4):CD Leak AM, Cooper J, Dyer S et al. (1994). The Northwick Park Neck Pain Questionnaire, devised to measure neck pain and disability. Br J Rheumatol, 33(5): Levine DW, Simmons BP, Koris MJ et al. (1993). A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am, 75(11): Naeser MA. (2006). Photobiomodulation of pain in carpal tunnel syndrome: review of seven laser therapy studies. Photomed Laser Surg, 24: Ostelo RW, Deyo RA, Stratford P et al. (2008). Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine (Phila Pa 1976), 33(1): Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 21

22 Ozyurekoglu T, McCabe SJ, Goldsmith LJ et al. (2006). The minimal clinically important difference of the Carpal Tunnel Syndrome Symptom Severity Scale. J Hand Surg Am, 31(5): Salaffi F, Stancati A, Silvestri CA et al. (2004). Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Eur J Pain, 8(4): Shapiro BE, Preston DC. (2009). Entrapment and compressive neuropathies. Med Clin North Am, 93(2): , vii. Sim J, Jordan K, Lewis M et al. (2006). Sensitivity to change and internal consistency of the Northwick Park Neck Pain Questionnaire and derivation of a minimal clinically important difference. Clin J Pain, 22(9): Tumilty S, Munn J, McDonough S et al. (2010). Low level laser treatment of tendinopathy: a systematic review with meta-analysis. Photomed Laser Surg, 28(1):3-16. World Association of Laser Therapy. (2010). Recommended treatment doses for low level laser therapy (revised April 2010). Available online at: nu/dosage-recommendations.html. Last accessed June Yousefi-Nooraie R, Schonstein E, Heidari K et al. (2008). Low level laser therapy for nonspecific low-back pain. Cochrane Database Syst Rev, (2):CD Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

23 Technology Evaluation Center Blue Cross and Blue Shield Association 225 North Michigan Avenue Chicago, Illinois Registered marks of the Blue Cross and Blue Shield Association, an Association of Independent Blue Cross and Blue Shield Plans Registered trademark of Kaiser Permanente 2010 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.