JACM

THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 00, Number 00, 2019, pp. 1–9
ª Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2019.0169

Laser Acupuncture for Carpal Tunnel Syndrome:

A Single-Blinded Controlled Study
Chi-Wen Juan, MD,1,2,* Ming-Hong Chang, MD, PhD,3,4 Tsung-Hsing Lin, MD,1,*
Kai-Lin Hwang, MS,5 Tieh-Cheng Fu, MD, PhD,6,7 Po-Hsuan Shih, MD,8,9
Ching-Mao Chang, MD, PhD,10,11 and Chun-Pai Yang, MD, PhD12,13
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Abstract
Objectives: This study aimed to compare the efficacy of laser acupuncture (LA) treatment with that of
placebo LA treatment in patients with idiopathic, mild-to-moderate carpal tunnel syndrome (CTS), as measured
by subjective symptom assessments and objective changes in nerve conduction studies (NCSs).
Design: A randomized, single-blinded, controlled study.
Settings: A Teaching Hospital in the Taichung, Taiwan between March 2013 and November 2013.
Subjects: 84 consecutive treatment-naive patients with CTS.
Interventions: Participants were randomly divided into two treatment arms: (1) LA, administered at tradi-
tional Chinese acu-points on the affected side, once a day, 5 times a week, for 4 weeks (N = 43); and (2) placebo
LA, administered using the same device and protocol, with the LA device switched off (N = 41).
Outcome measures: Patients completed the Global symptom score (GSS) at baseline and two and four weeks
later. The primary outcome was changes in GSS. NCSs were performed at baseline and repeated at the end of
the study as a secondary outcome.
Results: There was a significantly greater reduction in GSS in the LA group than in the placebo group at week
2 (-9.30 – 4.94 vs. -2.29 – 4.27, respectively, P < 0.01) and at week 4 (-10.67 – 5.98 vs. -2.90 – 5.61, respec-
tively, P < 0.01). However, NCSs did not show significant difference between the two groups.
Conclusions: LA may be more effective than placebo LA in the treatment of mild-to-moderate idiopathic CTS in
terms of subjective measurement. For patients who fear needle-based treatment, such as acupuncture or local
injections, or those who do not opt for early surgical decompression, LA treatment can be considered as an effective
and alternative form of acu-points stimulation therapy.

Keywords: low-level laser, laser acupuncture, carpal tunnel syndrome

1
Department of Emergency Medicine, Kuang Tien General Hospital, Taichung, Taiwan.
2
Department of Nursing, HungKuang University, Taichung, Taiwan.
3
Section of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan.
4
Department of Neurology, National Yang-Ming University, Taipei, Taiwan.
5
Department of Public Health, Chung Shan Medical University, Taichung, Taiwan.
6
Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan.
7
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
8
Department of Chinese Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
9
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
10
Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
11
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
12
Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan.
13
Department of Nutrition, Huang-Kuang University, Taichung, Taiwan.
*These authors contributed equally to this work.

1
 2 JUAN ET AL.
Introduction
C arpal tunnel syndrome (CTS) is an entrapment
neuropathy of the median nerve in the wrist. The diag-
nosis is based on clinical symptoms and specific physical
signs and is confirmed by electrophysiologic measure-
ments.1–4 Patients complain of pain or paresthesia involving
the fingers innervated by the median nerve and weakness of
thumb abduction. The classical symptoms are usually worse
at night, awaken the patients, and are often relieved by
shaking the hands repeatedly. Although several treatment
modalities are routinely used, there is no consensus for the
best management for CTS.5–7
Surgical decompression, often considered the definitive
solution, yields good results in only 75% of cases.1,6,8,9 Of the
nonsurgical treatments, a local injection of steroids has been
shown to provide short-term symptomatic relief; however, a
mechanical or chemical nerve injury can occur.1,6,9,10 Wrist
splints may be effective; nevertheless, the discomfort and
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restriction of hand activity hinders the patient’s ability to
work or perform daily activities.1,3,6,8 Oral steroids are more
effective than nonsteroidal anti-inflammatory drugs and di-
uretics; whereas, they have side effects.11,12 Since the stan-
dard treatments for CTS are not fully satisfactory, other
treatment modalities need to be further evaluated.
Laser acupuncture (LA) is defined as the stimulation of
traditional acupuncture points by using low-level intensity
(class IIIb laser: 5–500 mW, red beam or near infrared wave-
length, 600–1000 nm), nonthermal, noninvasive, and painless
laser irritation.13,14 Both acupuncture and LA are the non-
pharmacological and nonsurgical treatments for alleviating
FIG. 1. CONSORT diagram of
the study flow.
pain15–19; however, LA is one noninvasive treatment than
acupuncture for those patients who feared it or had the potential
risk for infection. Hence, LA may have the noninvasive ad-
vantage with wide acceptation.
Compared with needle-based acupuncture, low-level laser
therapy (LLLT) can be used for almost all patients, re-
gardless of platelet count and coagulation status; more im-
portantly, it does not involve pain or fear of needles.
Further, it is easier to achieve full blinding in LA clinical
trials than in needle acupuncture studies, particularly when
making comparisons.6,14 Nevertheless, seldom studies re-
ported the LA efficacy for CTS till this day.
Hence, we want to compare the efficacy of LA treatment
with that of placebo LA treatment in patients with mild-to-
moderate CTS by using subjective, self-reported symptom-
atic outcomes and objective electrophysiologic evaluations.
Materials and Methods
Study design and subjects
The CTS subjects were screened and enrolled from the
neurological outpatient department of Kuang-Tien General
Hospital. The recruited patients were randomly divided into
two groups of ‘‘LA Group’’ and ‘‘Placebo LA Group’’ in
this randomized, single-blinded, controlled study (Fig. 1).
Ethics statement
The study was approved by the Institutional Review
Board of Kuang Tien General Hospital (IRB9827). Written
 LASER ACUPUNCTURE FOR CARPAL TUNNEL SYNDROME
informed consent was obtained from each patient, and it was
registered with the Australian New Zealand Clinical Trials
Registry (ACTRN12613001065785).
Inclusion criteria
Treatment-naive patients with CTS, aged 20–65 years, were
enrolled in this study. The inclusion criteria were based on a
combination of clinical and electrodiagnostic findings of idi-
opathic mild-to-moderate CTS. The CTS diagnosis was based
on the presence of at least one of the following symptoms: (1)
pain, numbness, or paresthesia in the median nerve distribu-
tion; (2) precipitation of these sensory complaints by forceful
or repetitive hand use, which could be relieved by resting,
rubbing, and shaking of the hands; and (3) awakening from
sleep due to such sensory symptoms. The diagnosis was often
supported by a positive Tinel’s or Phalen’s test.
All patients with clinically diagnosed CTS demonstrated
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median neuropathy at the wrist, confirmed by the presence
of one or more of the following standard electrophysiologic
criteria: (1) prolonged distal motor latency (DML) to the
abductor pollicis brevis (APB) (abnormal ‡4.7 ms; wrist to
APB, 8 cm); (2) prolonged antidromic distal sensory latency
(DSL) to the second digit (abnormal ‡3.1 ms; wrist to index
finger, 14 cm); and (3) prolonged antidromic wrist-palm
sensory nerve conduction velocity (W-P SNCV) at a dis-
tance of 8 cm (W-P SNCV, abnormal <45 m/s).20
Mild CTS referred to a decreased conduction velocity at
the palm-wrist segment and delayed DSL, with normal
median sensory nerve action potential (SNAP) amplitude
and compound muscle action potential (CMAP) amplitude
of the APB. Moderate CTS referred to an abnormally de-
layed DML and DSL, with either decreased median SNAP
amplitude or decreased CMAP amplitude of the APB
muscle. Severe CTS patients referred to the presence of
either fibrillation potentials or re-innervation on needle
electromyography in the APB muscle.11,12
Exclusion criteria
Patients were excluded if any of the following were pres-
ent: (1) Symptoms occurring less than 3 months before the
study (to exclude patients who might have spontaneous res-
olution of symptoms); (2) severe CTS that had progressed to
visible muscle atrophy; (3) clinical or electrophysiologic
evidence of accompanying conditions that could mimic CTS
or interfere with its evaluation, such as cervical radiculo-
pathy, proximal median neuropathy, or significant poly-
neuropathy; (4) evidence of obvious underlying etiologic
factors of CTS such as diabetes mellitus, rheumatoid arthritis,
hypothyroidism (acromegaly), pregnancy, alcohol abuse or
drug usage (steroids or drugs acting through the central ner-
vous system), and suspected malignancy or inflammation or
autoimmune disease documented as underlying causes of
CTS; or (5) cognitive impairment interfering with the sub-
ject’s ability to follow instructions and describe symptoms.
Blinding and randomization
This was a single-blinded trial, in which patients could
not tell the difference between the real LA (using invisible,
near-infrared laser emission and red light) and placebo LA
(using red light). There was little chance of communication
3
between patients because most of them came for treatment
at different times. The outcome measurements were evalu-
ated by blinded assessors, and the statistical analyzers were
not involved in the patients’ clinical management; thus, they
were unaware of the patient locations.
However, the LA practitioners were not blinded. Patients
were randomly allocated to start with either real or sham LA
treatment. The randomization list was compiled by an ex-
ternal physician and was not divulged to the study practi-
tioners or patients. The same physician prepared a series of
sealed, sequentially numbered envelopes containing the
treatment assignments. When a patient was found to fulfil
the inclusion criteria, the study physician would open the
envelope to reveal the patient’s group allocation. This pro-
cedure assured that randomization would not be influenced
by the physicians, outcome assessors, or patients.
Electrophysiologic assessments
The electrophysiologic assessments were performed by
using an electromyography (EMG)/nerve conduction study
(NCS) system (Nicolet Viking IV, Madison, WI). Motor and
sensory NCSs were performed across the carpal tunnel by
using the standard techniques of supramaximal percutaneous
stimulation and surface electrode recording. DML, DSL,
motor nerve conduction velocity (MNCV), CMAP and
SNAP amplitudes, and W-P SNCV were measured by using
the methods described by Delisa et al.21
The EMG recording was made with the filter band pass at
2–10 Hz, a sweep speed of 2 ms/cm, and an amplifier gain
adjusted for full reviewing of the CMAP. For the mea-
surement of SNAP, the instrument settings were as fol-
lows: filters, 20–10 kHz; sweep, 2 ms/cm; and gain, 10–
20 mV/cm. We used the following electrophysiologic pa-
rameters as our secondary outcome: DML, CMAP, MNCV,
DSL, SNAP, and W-P SNCV. The skin temperature of the
forearm and wrist were maintained at >32C throughout the
measurements. The electrophysiologic assessments were
conducted at baseline and were repeated again 4 weeks later.
Laser device and LA intervention
In our study, LA treatment indicates the use of LLL (class
IIIb lasers, 400 mW, near-infrared, continuous wavelength,
810 nm, LaserPenR; RJ-LASER, Germany) at traditional
Chinese acu-points as PC-7 (Daling) and PC-6 (Neiguan) on
the affected side. LA consisted of treatments once per day
for 5 consecutive days, followed by a 2-day break, with a
total of 20 sessions in a 4-week period. Each laser stimu-
lation treatment was performed in a continuous wave mode
for 1 min. The energy transferred to the skin during a
treatment of 1 min was up to *24 J/cm2.
For the placebo LA treatment, the same device with a red
light was pasted on the acu-points in the same way, using
the same protocol as for the active laser stimulation, but the
laser apparatus was not switched on. It was impossible for
the patients to differentiate between active and placebo laser
because the same red light was visible with or without the
invisible low-level laser in both groups.
Measurement of primary and secondary outcomes
Global Symptom Score (GSS) was used as a primary
outcome in this trial. Clinical symptoms were rated from 0
 4 JUAN ET AL.

(no symptoms) to 10 (very severe symptoms) in the fol-
lowing 5 symptom categories: pain, numbness, tingling,
weakness/clumsiness, and nocturnal awakening.11,12,22,23
Each patient was directly questioned, and each score was
based on the patient’s subjective answers. Therefore, the
maximum score was 50 (most severe symptoms), and the
minimum score was 0 (absence of symptoms). To ensure
consistency, the evaluating physician who scored the main
outcome measure, GSS, was the same person on each oc-
casion for each patient and was blinded to the type of
treatment. The patients completed the GSS standard ques-
tionnaires at baseline and 2 and 4 weeks later.
The following electrophysiologic parameters were used
as secondary outcome: DML, CMAP, MNCV, DSL, SNAP,
and W-P SNCV. Additional secondary outcome measures
were the following treatment efficacy grades: good im-
provement, defined as a >50% reduction in GSS; moder-
ate improvement, defined as a 30%–50% reduction in GSS;
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Repeated-measures analysis of variance (ANOVA) was used
to compare the values of the subjective symptom’s assessment
over time between the groups.
All hypothesis tests were two tailed, and a level of sig-
nificance was set at 0.05. With a two-sided test, significance
level of 0.05, power of 80%, standard deviation of 4.5, and
20% drop-out rate, at least 45 subjects per treatment were
required to detect a difference of 3.0 in mean reduction of
GSS from baseline between the two groups. All statistical
analyses were performed by using the SPSS software for
Windows, Version 15.0 (SPSS, Inc., Chicago, IL).
Results
Patients’ demographics
There were no significant differences in age, sex, duration
of symptoms, GSS, and subjective symptom assessments
such as numbness, pain, paresthesia, weakness, and noc-

lost to follow-up, defined as <30% reduction; and treatment
failure, defined by the presence of APB muscle wasting or
receiving surgery or other conservative treatment.
Adverse events (AEs) and serious AEs (SAEs) with side
effects were collected at each treatment session.
Statistical analysis
The last observation carried forward method was used to
impute missing data, and the intent-to-treat analysis princi-
ple was adopted. If patients reported symptoms in both
hands, we included the more affected hand with a higher
GSS for data analysis.
The means and standard deviations were calculated for all
subjects in each group, for each parameter. The independent
two-sample t test was performed to compare the changes in the
objective EMG/NCV findings and subjective symptoms as-
sessment between the two groups for the baseline, 2-week, and
4-week evaluations. The paired t test was performed to com-
pare the week-2 and week-4 data for the objective EMG/NCV
findings and subjective symptoms assessment with the base-
line data within each treatment group. For the five main
symptom scores of the GSS and six measures of the NCS,
Bonferroni adjustment was made to control for type I errors.
turnal awakening at baseline between the two treatment
groups (Table 1).
Changes from baseline clinical outcomes
at weeks 2 and 4
Both groups showed a significant improvement in the GSS,
numbness, and weakness ( p < 0.05), and only the real LA
group showed a significant improvement in pain, paresthesia,
and nocturnal awakening assessment ( p < 0.01) at weeks 2 and
4 when compared with baseline. The real LA group also
showed a significantly greater improvement in the GSS,
numbness, pain, and nocturnal awakening than the placebo LA
group ( p < 0.01) at weeks 2 and 4, and in paresthesia at week 2
( p < 0.01). No significant difference was observed between the
two groups in changes in the degree of weakness from baseline
during the study period. The repeated-measurement ANOVA
results indicated a significant difference ( p = 0.009) in the GSS
between the groups over time (Table 2 and Fig. 2).
A sensitivity analysis for missing data with the worst case
scenario was performed for week 4. The condition of the
early discontinued LA patient was assumed to be worse than
that at baseline, and the three placebo subjects had improved
outcomes at week 4 when compared with baseline. All the

Table 1. Demographic Characteristics and Subjective Symptom Assessments at Baseline for Both Groups
Laser (N = 43) Placebo (N = 41)
Mean SD Mean SD Sig.
Age (years) 41.02 5.57 40.83 4.77 NS
Gender, n (%)
Female 40 (93.0%) 38 (92.7%) NS
Male 3 (7.0%) 3 (7.3%)
Duration of symptoms (month) 7.09 3.07 6.54 1.87 NS
Global Symptom Score 16.19 9.07 15.68 8.65 NS
Subjective symptom assessments
Numbness 5.35 1.73 4.98 2.02 NS
Pain 3.88 2.47 3.10 2.10 NS
Paresthesia 3.23 2.49 3.05 2.20 NS
Weakness 1.53 2.04 2.07 1.74 NS
Nocturnal awakening 2.14 2.28 2.51 2.43 NS
p-Value by two independent-sample t tests or Fisher’s exact test when appropriate.
NS, no significance; SD, standard deviation; Sig., significance.
 LASER ACUPUNCTURE FOR CARPAL TUNNEL SYNDROME 5

Table 2. Change from Baseline in Clinical Assessments for Both Groups at Weeks 2 and 4
GSS Numbness Pain Paresthesia Weakness Nocturnal awakening
Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD
Week 2
Laser -9.30 4.94* -2.60 1.28* -1.67 1.73* -2.00 1.89* -0.79 1.64* -2.05 2.37*
Placebo -2.29 4.27* -0.88 1.95** 0.02 1.23 -0.44 1.94 -0.73 1.70** 0.24 2.64
p <0.001 <0.001 <0.001 <0.001 NS <0.001
Week 4 by LOCF
Laser -10.67 5.98* -3.02 1.46* -2.37 1.94* -2.02 1.83* -1.16 1.77* -2.05 2.37*
Placebo -2.90 5.61* -1.10 2.08* 0.15 1.73 0.46 5.99 -0.76 1.85** -0.41 2.05
p <0.001 <0.001 <0.001 NS NS 0.007
Week 4 by sensitivity analysis
Laser -10.49 6.49* -2.98 1.58* -2.33 2.02* -1.98 1.91* -1.12 1.83* -2.05 2.37*
Placebo -3.78 5.71* -1.24 2.07* -0.05 1.79 0.27 6.02 -1.00 1.76* -0.76 1.76
p <0.001 <0.001 <0.001 NS NS 0.036
Values are mean and standard deviation of change from baseline (data at week 2 or 4–baseline). Sig.: p-value by two independent-sample
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t tests using Bonferroni adjustment to compare the two groups.

*p < 0.01; **p < 0.05 values of week 2 or 4 were significantly different from baseline by using the paired t test within each group with
Bonferroni adjustment.
GSS, Global Symptom Score; LOCF, last observation carried forward; NS, no significance; SD, standard deviation.

conclusions remained the same as the last observation car-
ried forward approach (Table 2 and Fig. 3).
Electrophysiologic outcomes at baseline and week 4
No significant difference in the baseline electrophysiologic
assessments was observed between the two groups (Table 3).
After a 4-week treatment, the changes from baseline of all
electrophysiologic assessments were not significantly differ-
ent between the two groups, and none of the after-treatment
assessments were significantly different from those at base-
line within each group ( p > 0.05) (Table 3).
good improvement were significantly different between the
two groups at week 2 (4.7%, 18.6%, and 76.7% for the real
LA group, and 65.9%, 14.6%, and 19.5% for the placebo LA
group, respectively [p < 0.001]) and at week 4 (2.3%, 9.3%,
and 88.4% vs. 51.2%, 17.1%, and 31.7%, respectively
[p < 0.001]) (Table 4).
In addition, AEs and SAEs were not reported from the
participants in either group for all of the sessions in this
study.
Discussion

Patients’ improvement rates In this study, the patients with CTS who underwent the
real LA treatment had a significantly greater, clinically
Compared with the baseline levels, the percentages of relevant improvement in terms of the primary outcome
patients with treatment failure, moderate improvement, and measure, GSS, at weeks 2 and 4, than that of the patients

FIG. 2. Means with standard error of the total Global

Symptom Score with LOCF for the real and sham laser
acupuncture groups over time. A significant difference
( p = 0.009) was observed between the two groups by
repeated-measures ANOVA. **p < 0.01 by the paired t test
with Bonferroni adjustment for p-value when compared
with the baseline level within each group. ANOVA, analysis
of variance; LOCF, last observation carried forward.
FIG. 3. Means with standard error of the total Global
Symptom Score with sensitivity analysis for the real and sham
laser acupuncture groups over time. A significant difference
( p = 0.014) was observed between the two groups by repeated-
measures ANOVA. **p < 0.01 by the paired t test with Bon-
ferroni adjustment for p-value when compared with the base-
line level within each group. ANOVA, analysis of variance.
 6 JUAN ET AL.

Table 3. Electrophysiologic Assessments at Baseline and After Treatment for Both Groups
Laser Placebo
Baseline After treatment Baseline After treatment
Electrodiagnostic variable,
with normal result Mean SD Mean SD Mean SD Mean SD Sig.
DML (ms), <4.7 5.23 1.20 5.20 0.59 5.27 1.07 5.41 1.06 NS
CMAP (mv), >6.5 7.07 2.64 7.20 2.36 7.92 2.14 8.03 2.19 NS
MNCV (mv), >50 53.30 3.90 53.61 3.65 52.40 3.41 52.34 2.60 NS
DSL (ms), <3.1 3.46 0.67 3.38 0.71 3.36 0.57 3.40 0.41 NS
SNAP (mv), >15 18.00 5.39 18.35 8.85 18.06 6.30 18.87 8.14 NS
W-P SNCV (m/s), >45 40.35 5.25 41.62 4.78 40.57 4.63 41.94 3.67 NS
None of the after-treatment assessments were significantly different from those at baseline within each group using the paired t test. Sig.:
The change from baseline (after treatment—baseline) was compared between groups by using the independent two-sample t test.
CMAP, compound muscle action potential; DML, distal motor latency; DSL, distal sensory latency; MNCV, motor nerve conduction
velocity; NS, no significance; SD, standard deviation; Sig., significance; SNAP, sensory nerve action potential; W-P SNCV, wrist-palm
sensory nerve conduction velocity.
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who underwent the placebo LA treatment. This result was on acupuncture points on the affected hands, and infrared
also supported by the higher percentage of >50% improve- gallium arsenide (GaAs) (904 nm, pulsed, 9.4 W) on acu-
ment in the actual treatment group than in the placebo group puncture points located at the elbow, shoulder, upper back,
at weeks 2 and 4 for the subjective measurement of GSS; and cervical paraspinal areas. Significant improvement was
however, the before-after treatment difference in the as- observed in the pain level, sensory latency, and Phalen’s and
sessment with objective measurement of NCSs between the Tinel’s test results after the real LLLT, but not after the sham
two groups was not significant. The strength of this study is treatment.
that both clinical and electrophysiologic assessments based However, no significant differences were observed in any
on valid and standard measures were used. The application objective evaluation. Irvine et al. compared the effects of
of LLLT on the traditional Chinese acu-points was clearly LLLT therapy with those of a sham laser therapy by using a
described in the treatment protocols, making our study re- Ga-Al-As diode laser with a wavelength of 860 nm.25 A
producible. total dose of 6 J/cm2 given over 15 min to the area sur-
The clinical evidence of the efficacy of LLLT for the rounding the carpal tunnel was delivered three times a week,
treatment of idiopathic CTS is controversial and consists of for 5 weeks. The investigators did not find any significant
studies presenting ambiguous conclusions.21,24–30 Naeser difference in the CTS symptoms, hand function, or the NCS
et al. investigated the effects of real or sham LLLT plus findings between the control and treated groups. Evcik et al.
microampers transcutaneous electric nerve stimulation compared the efficacies of LLLT and sham laser therapy by
(TENS) in patients with CTS.24 The investigators used a using a Ga-Al-As diode laser with a wavelength of
helium neon laser (632.8 nm, continuous wave, 15 mW) 830 nm.26 Their patients underwent laser therapy over the
carpal tunnel area at the wrist with a power output of 7 J/
point for 2 points, once a day, for 10 treatment sessions.
Table 4. Improvement Rates from Baseline The investigators found positive effects on the hand and
to Weeks 2 and 4 for Both Groups pinch grip strength that were superior to the placebo treat-
ment; however, there was no difference in the pain relief and
Laser Placebo functional capacity. Chang et al. placed an 830-nm laser
n % n % p (10 Hz, 50% duty cycle, 60 mW, 9.7 J/cm2) directly above
the transverse carpal ligament, which is between the pisi-
Week 2 form and navicular bones of the wrist.27 After 2 weeks of
Good improvement 33 76.7 8 19.5 <0.001 treatment, no significant differences were found in the grip
Moderate improvement 8 18.6 6 14.6 strength or in the symptoms and functional assessments.
Treatment failure 2 4.7 27 65.9 However, there were statistically significant differences in
Week 4 by LOCF these variables at the 2-week follow-up.
Good improvement 38 88.4 13 31.7 <0.001
For the NCS findings, there was no statistically significant
Moderate improvement 4 9.3 7 17.1
Treatment failure 1 2.3 21 51.2 difference between the groups after treatment and at the 2-
Week 4 by sensitivity analysis week follow-up. Shooshtari et al. used a low-power laser
Good improvement 38 88.4 13 31.7 <0.001 (400 nm, pulse wave, 9–11 J/cm2) at the carpal tunnel area
Moderate improvement 4 9.3 10 24.4 for 15 sessions, and they found no difference in the symp-
Treatment failure 1 2.3 18 43.9 toms or grip strength; however, they did note a slight im-
provement in the electrophysiologic findings with LLLT.28
A reduction in the Global Symptom Score of more than 50% was The controversial results in different clinical studies may
defined as good improvement, 30%–50% as moderate improve-
ment, and less than 30% as treatment failure. p-Value by Fisher’s be related to various factors such as the study designs, study
exact test. populations, outcome evaluations, and treatment parameters.
LOCF, last observation carried forward. Regarding the treatment device and application procedures,
 LASER ACUPUNCTURE FOR CARPAL TUNNEL SYNDROME
different types of lasers may have different effectiveness in
wide variations of therapeutic parameters, such as the
wavelength, energy density, duration of treatment, number of
treatments, and mode of delivery.13,14,31,32 The laser mode
used in our study differed from the designs mentioned earlier.
In addition, the energy density ( J/cm2) reported in our study
(24 J/cm2) was stronger than in any of the previous studies.
Further, the positive effect of LLLT when used to stimulate
the acupuncture points as defined in the Channels theory of
Traditional Chinese Medicine, an effect that was observed in
our study as well as in the trial of Naeser et al.,24 may explain
the importance of the stimulating sites. Traditional acupuncture
points have been reported to have a lower electrical impedance
and higher capacitance compared with adjacent controls.33 The
dosage and treatment time with the 810 nm laser in the stim-
ulation of the acu-points may be sufficient to provide an ef-
fective energy for resolution of the clinical symptoms.
LA might provide a new treatment modality and bring
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into perspective an integrated Western and Traditional
Chinese Medicine. In the future, further comparisons should
be made with different types of laser settings and stimu-
lating locations to provide practitioners better therapeutic
programs for patients with CTS.
The efficacy of LLLT has been demonstrated in a variety
of medical conditions; some proposed mechanisms have been
documented and include the suppression of inflammation,
tissue repairing and regeneration, and facilitating nerve re-
covery by stimulating regeneration.34,35 Previous studies have
also shown that laser energy would increase the ATP pro-
duction, improve cellular respiration, and increase the levels
of serotonin and endogenous opioids.36,37 In our study, there
was significant improvement in the subjective GSS; however,
there was no statistically significant before-after difference in
the NCS findings between or within the two groups.
The discrepancy between the clinical improvement and
objective change in the NCS findings has two possible ex-
planations. First, previous studies have shown that LLLT can
induce a reversible blockade of neurotransmission in the A-
delta and C fibers.38 If the small fibers were predominantly
affected by the LLLT, this would allow a decrease in the pain
transmission, leading to symptoms relief without accompa-
nying objective changes in the NCSs, because the standard
NCS techniques provide information only on the largest and
fastest-conducting myelinated nerve fibers. Second, the post-
treatment NCS may have been obtained too early to detect an
obvious change in the findings.
This is similar to the postoperative findings for CTS; there
was a rapid subjective improvement postsurgery, with a
delayed improvement in the NCS parameters.39–42 A long-
term follow-up using NCSs might be helpful to detect the
delayed effects of LLLT on the affected nerves in CTS.
No patients in either group reported any adverse effects
with regards to the LA. This is in line with reports on the
safety of LLLT.13 In our previous study, we demonstrated
that needle acupuncture was as effective as short-term low-
dose prednisolone at 1 month, and it had better outcomes at
12 months in patients with mild-to-moderate CTS.22,23
However, during the recruitment phase, some of the subjects
expressed fear of needle acupuncture procedures and were
unwilling to take part in the study. In addition, since the
acupuncture intervention is more invasive (skin penetration
with a needle) than the control group intervention (pills),
7
placebo effects may have contributed to the between-group
difference observed in that study.
In this study, the clinical effect of LA for CTS was likely
due to the combination of the actual biological effect of
LLLP on the acu-points, and the nonspecific effects, such as
nearly daily contact with the physicians, or patient expec-
tations of the treatment effects.43,44 Blinding patients to the
placebo-laser setting in this study was used to rule out a
possible placebo effect or biases caused by expectations and
subjective assessments. Indeed, some of the patients treated
with sham laser experienced remarkable clinical improve-
ment, which is in line with previous studies.25,28
Based on these results, we believe that placebo LA can
serve as a valid control procedure for evaluating specific LA
effects. The results in our study demonstrated that the pa-
tients with real LA treatment had significant improvement in
the subjective symptom assessment compared with the pa-
tients with placebo LA treatment.
The missing data on week 4 for the 4 early discontinued
subjects were originally replaced with the data obtained on
week 2 for analysis. Since significant differences were ob-
served between the two groups for most of the clinical as-
sessments at week 4 with the last observation carried forward,
a sensitivity analysis with the worst case was performed as
suggested by the reviewers to verify the robustness of such
methods. The condition of the LA patient who failed to return
at week 4 was assumed to be worse than that at baseline; all
assessments were replaced with the values of baseline plus 2,
that is, GSS plus 10. On the contrary, the condition of the
three early discontinued placebo subjects was assumed to be
better than that at baseline, with all data replaced with the
baseline values minus 2, that is, GSS minus 10.
The results are presented in Tables 2, 4, and Figures 2, 3
given next and all the conclusions remained the same as the
last observation carried forward approach. The results from
repeated-measurement ANOVA also indicated a significant
difference ( p = 0.014) in the GSS score between the groups
over time. Although the number of early withdrawals was
greater in placebo than in LA group, 3 versus 1, all the 3
placebo subjects actually had a worse condition at week 2
than that at baseline. Now we assumed that their conditions at
week 4 improved even better than those at baseline instead of
being the same as week 2, and the difference between the two
groups remained significant. This result implies that the
treatment effect, indeed, existed and the impact of missing
data would not alter the conclusion significantly in this study.
This study has several limitations that are worth noting, each
of which points toward improvements that can be considered
in a future study. First, only the short-term effectiveness of
LLLT was evaluated, and evaluations of long-term beneficial
effects are necessary. Second, although patients were unaware
of their treatment group, the physicians were not blinded to the
patients’ treatment assignment. Thus, we are not sure whether
the degree of the observed change was due to nonspecific
effects in this regard.
Third, the natural history of CTS is not necessarily pro-
gressive; patients may even spontaneously recover if they
change their lifestyle or risk factor-related behavior after they
recognize their disease characteristics.28,45 However, the su-
periority of the real over the placebo LA in our study could
not be explained by spontaneous improvement, because when
using randomization, spontaneous improvement would occur
 8 JUAN ET AL.
evenly in both groups. Fourth, the treatment protocol required
more study visits. Each subject had to visit the physician 5
times per week for 4 weeks. This limited the number of
subjects who were willing to participate. Fifth, the GSS was
recorded as the only affected side with higher severity in this
study, and we did not include the bilateral hand to analyze. It
may be one limitation for efficacy evaluation, so we add this
deficiency in the limitation. We may include the bilateral
CTS with both hands analysis in future.
Conclusion
Despite these limitations, this randomized, single-blinded
controlled study indicated that LA is more effective than pla-
cebo LA in the treatment of mild-to-moderate idiopathic CTS
in terms of subjective measurement. Therefore, we recommend
that LA treatment be considered as an alternative therapy for
those who fear needle-based treatment, such as acupuncture or
Downloaded by East Carolina University from www.liebertpub.com at 09/11/19. For personal use only.
local injections, or those who do not opt for early surgical
decompression. Future studies should consider comparisons
between LA and acupuncture or other conservative treatments,
and they explore the underlying mechanisms and biophysical
effects of LA on the nerve tissue regeneration in CTS. Treat-
ment frequency could hamper translation to clinical practice
and may be one limitation for LA efficacy.
Authors’ Contributions
C.W.J., T.H.L., C.M.C., and C.P.Y. were responsible for
the study concept and design, modification of the study
design, and review and interpretation of the data. C.W.J.,
T.H.L., C.M.C., and C.P.Y. were responsible for drafting the
article. M.H.C., C.L.H., T.C.L., and K.L.W. made modifi-
cations to the study design and revised the article. C.W.J.,
T.H.L., and T.C.L. contributed to the collection and analy-
sis. M.H.C., C.L.H., C.M.C., and C.P.Y. contributed to the
interpretation of data and revised the article. All authors
read and approved the final article.
Ethics Approval
The study was approved by the Institutional Review
Board of Kuang Tien General Hospital, Taichung, Taiwan
(IRB9827). Written informed consent was obtained from
each patient.
Author Disclosure Statement
All authors listed in the article have contributed suffi-
ciently to it, have approved the article, and declare that they
have no conflicts of interest to declare.
Funding Information
This study was supported by a grant from Kuang Tien
General Hospital, Taichung, Taiwan, and NSC-99-2628-B-
075A-008-MY2.
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Address correspondence to:
Chun-Pai Yang, MD, PhD
Department of Neurology
Kuang Tien General Hospital
No. 117, Shatian Road
Shalu District
Taichung 433
Taiwan
E-mail: neuralyung@gmail.com
Ching-Mao Chang, MD, PhD
Center for Traditional Medicine
Taipei Veterans General Hospital
No. 201, Section 2, Shih-Pai Road
Beitou District
Taipei 112
Taiwan
E-mail: magicbjp@gmail.com