ArticlePDF AvailableLiterature Review

Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis

Authors:

Abstract and Figures

Background: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Low-level laser therapy (LLLT), an emerging nonpharmacological treatment, has been used for relieving musculoskeletal or neuropathic pain. Objective: The objective of this review and meta-analysis was to determine the efficacy of LLLT on patients with fibromyalgia. Study design: This study involved systematic review and quantitative meta-analysis of published randomized controlled trials (RCTs). Setting: This study examined all RCTs evaluating the effect of LLLT on fibromyalgia. Methods: We performed a systematic review and meta-analysis of RCTs evaluating the effect of LLLT on patients with fibromyalgia. PubMed, EMBASE, and the Cochrane Library were searched for articles published before August 2018. RCTs meeting our selection criteria were included. The methodological quality of the RCTs was evaluated according to the Cochrane risk-for-bias method. Review Manager version 5.3 was used to perform the meta-analysis. The primary outcomes were the total scores on the Fibromyalgia Impact Questionnaire (FIQ), pain severity, and number of tender points. The secondary outcomes were changes in fatigue, stiffness, anxiety, and depression. Standardized mean difference (SMD), 95% confidence intervals (CI), and P values were calculated for outcome analysis. Results: We identified 9 RCTs that included 325 fibromyalgia patients undergoing LLLT or placebo laser treatment with or without an exercise program. The meta-analysis showed that patients receiving LLLT demonstrated significantly greater improvement in their FIQ scores (SMD: 1.16; 95% CI, 0.64-1.69), pain severity (SMD: 1.18; 95% CI, 0.82-1.54), number of tender points (SMD: 1.01; 95% CI, 0.49-1.52), fatigue (SMD: 1.4; 95% CI, 0.96-1.84), stiffness (SMD: 0.92; 95% CI, 0.36-1.48), depression (SMD: 1.46; 95% CI, 0.93-2.00), and anxiety (SMD: 1.46; 95% CI, 0.45-2.47) than those receiving placebo laser. Furthermore, when compared with the standardized exercise program alone, LLLT plus the standardized exercise program provided no extra advantage in the relief of symptoms. On the other hand, the results of the only RCT using combined LLLT/LED phototherapy showed significant improvement in most outcomes except for depression when compared to placebo. When compared with pure exercise therapy, combined LLLT/LED phototherapy plus exercise therapy had additional benefits in reducing the severity of pain, number of tender points, and fatigue. Limitations: There were some limitations in this review, mostly because of the low-to-middle methodological quality of the selected studies; for example, there was no clear allocation process and only patients were blinded in most studies. In addition, one study used per-protocol analysis with a 20% loss to follow-up. On the other hand, the differences in laser types, energy sources, exposure times, and associated medication status in these studies may have resulted in some heterogeneity. Conclusions: Our results provided the most up-to-date and relevant evidence regarding the effects of LLLT in fibromyalgia. LLLT is an effective, safe, and well-tolerated treatment for fibromyalgia. Key words: Low-level laser therapy, fibromyalgia, meta-analysis, FIQ, pain, tender points,exercise.
Content may be subject to copyright.
Background: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness.
Low-level laser therapy (LLLT), an emerging nonpharmacological treatment, has been used for
relieving musculoskeletal or neuropathic pain.
Objective: The objective of this review and meta-analysis was to determine the efficacy of LLLT
on patients with fibromyalgia.
Study Design: This study involved systematic review and quantitative meta-analysis of published
randomized controlled trials (RCTs).
Setting: This study examined all RCTs evaluating the effect of LLLT on fibromyalgia.
Methods: We performed a systematic review and meta-analysis of RCTs evaluating the effect of
LLLT on patients with fibromyalgia. PubMed, EMBASE, and the Cochrane Library were searched
for articles published before August 2018. RCTs meeting our selection criteria were included. The
methodological quality of the RCTs was evaluated according to the Cochrane risk-for-bias method.
Review Manager version 5.3 was used to perform the meta-analysis. The primary outcomes were
the total scores on the Fibromyalgia Impact Questionnaire (FIQ), pain severity, and number of
tender points. The secondary outcomes were changes in fatigue, stiffness, anxiety, and depression.
Standardized mean difference (SMD), 95% confidence intervals (CI), and P values were calculated
for outcome analysis.
Results: We identified 9 RCTs that included 325 fibromyalgia patients undergoing LLLT or
placebo laser treatment with or without an exercise program. The meta-analysis showed that
patients receiving LLLT demonstrated significantly greater improvement in their FIQ scores (SMD:
1.16; 95% CI, 0.64-1.69), pain severity (SMD: 1.18; 95% CI, 0.82-1.54), number of tender
points (SMD: 1.01; 95% CI, 0.49-1.52), fatigue (SMD: 1.4; 95% CI, 0.96-1.84), stiffness (SMD:
0.92; 95% CI, 0.36-1.48), depression (SMD: 1.46; 95% CI, 0.93-2.00), and anxiety (SMD: 1.46;
95% CI, 0.45-2.47) than those receiving placebo laser. Furthermore, when compared with the
standardized exercise program alone, LLLT plus the standardized exercise program provided no
extra advantage in the relief of symptoms. On the other hand, the results of the only RCT using
combined LLLT/LED phototherapy showed significant improvement in most outcomes except for
depression when compared to placebo. When compared with pure exercise therapy, combined
LLLT/LED phototherapy plus exercise therapy had additional benefits in reducing the severity of
pain, number of tender points, and fatigue.
Limitations: There were some limitations in this review, mostly because of the low-to-middle
methodological quality of the selected studies; for example, there was no clear allocation process
and only patients were blinded in most studies. In addition, one study used per-protocol analysis
with a 20% loss to follow-up. On the other hand, the differences in laser types, energy sources,
exposure times, and associated medication status in these studies may have resulted in some
heterogeneity.
Conclusions: Our results provided the most up-to-date and relevant evidence regarding
the effects of LLLT in fibromyalgia. LLLT is an effective, safe, and well-tolerated treatment for
fibromyalgia.
Key words: Low-level laser therapy, fibromyalgia, meta-analysis, FIQ, pain, tender points,
exercise
Pain Physician 2019: 22:241-254
Systematic Review
Low-Level Laser Therapy for Fibromyalgia: A
Systematic Review and Meta-Analysis
From: 1School of Medicine,
Taipei Medical University,
Taipei, Taiwan; 2Institute of
Epidemiology and Preventive
Medicine, College of Public
Health, National Taiwan
University; 3Cochrane Taiwan,
Taipei Medical University, Taipei,
Taiwan; 4Center for Evidence-
Based Health Care, Taipei
Medical University - Shuang Ho
Hospital, New Taipei City, Taiwan;
5Division of General Surgery,
Department of Surgery, School of
Medicine, College of Medicine,
Taipei Medical University, Taipei,
Taiwan; 6Division of General
Surgery, Department of Surgery,
Shuang Ho Hospital, Taipei
Medical University, New Taipei
City, Taiwan; 7Department of
Neurology, Shuang Ho Hospital,
Taipei Medical University, New
Taipei City, Taiwan; 8Department
of Neurology, School of
Medicine, College of Medicine,
Taipei Medical University,
Taipei, Taiwan; 9Department of
Neurology, Taipei Neuroscience
Institute, Taipei Medical
University, Taipei, Taiwan
Address Correspondence:
Yi-Chun Kuan, MD
Department of Neurology, Taipei
Medical University-Shuang Ho
Hospital, 291 Zhongzheng Rd,
Zhonghe District, New Taipei
City, 23561, Taiwan
E-mail: yckuang2@gmail.com
Disclaimer: Shu-Wei Yeh and
Chien-Hsiung Hong contributed
equally to this study. There
was no external funding in the
preparation of this manuscript.
Conflict of interest: Each author
certifies that he or she, or a
member of his or her immediate
family, has no commercial
association (i.e., consultancies,
stock ownership, equity interest,
patent/licensing arrangements,
etc.) that might pose a conflict of
interest in connection with the
submitted manuscript.
Manuscript received: 09-27-2018
Revised manuscript received:
10-06-2018
Accepted for publication:
11-05-2018
Free full manuscript:
www.painphysicianjournal.com
Shu-Wei Yeh, MD1, Chien-Hsiung Hong, MD1, Ming-Chieh Shih, MD2, Ka-Wai Tam, MD, PhD3-6,
Yao-Hsien Huang, MD4,7,8, and Yi-Chun Kuan, MD2-4,7-9
www.painphysicianjournal.com
Pain Physician 2019; 22:241-254 • ISSN 1533-3159
Pain Physician: May/June 2019: 22:241-254
242 www.painphysicianjournal.com
ing the use of LLLT in fibromyalgia. On the other hand,
since exercise therapies or physical therapies have been
proven to be beneficial to patients with fibromyalgia,
we also used meta-analysis to compare the effective-
ness of a standardized exercise program plus LLLT with
a standardized exercise program alone.
Methods
Selection Criteria
We reviewed RCTs evaluating the efficacy of LLLT
for fibromyalgia. We included trials that (a) compared
the results of LLLT and placebo laser therapy in patients
with fibromyalgia; (b) described the inclusion and ex-
clusion criteria for patient selection; and (c) reported
power, wavelength, and laser exposure duration. We
excluded trials that used a class IV laser because laser
class ≤ IIIB is considered therapeutic, whereas a class IV
laser causes tissue destruction. Furthermore, trials with
laser treatment focusing only on one joint or a specific
region of the body were excluded.
Search Strategy and Study Selection
We searched PubMed, EMBASE, and the Cochrane
Library for studies on fibromyalgia. The following MeSH
terms and Boolean operator were used: fibromyalgia
AND (laser OR low-level laser OR photobiomodulation
OR phototherapy). The “Related Articles” option in
PubMed was used to broaden the search. We applied no
language restrictions. The final search was performed
in August 2018. We selected studies on the basis of
the titles and abstracts meeting the selection criteria.
The systematic review described here was accepted by
PROSPERO, the online international prospective regis-
ter of systematic reviews of the National Institute for
Health Research (CRD42017079531).
Data Extraction
Two authors (SWY and CHH) independently se-
lected RCTs and extracted the relevant details: number,
age, and gender of participants; inclusion and exclusion
criteria; laser strategies; and outcome parameters. The
individually-recorded information of both reviewers
was compared, and a third reviewer (YCK) resolved any
discrepancies.
Methodological Quality Appraisal
The 3 aforementioned reviewers independently
evaluated the methodological quality of the RCTs ac-
cording to the Cochrane risk-for-bias method (12).
Fibromyalgia is a chronic disorder characterized
by widespread pain and tenderness. Patients
with fibromyalgia often suffer from fatigue,
sleep disturbance, and memory problems (1).
Neurological complaints such as paresthesia, blurred
vision, numbness, and weakness are also commonly
seen (1,2). Its estimated prevalence is 2.1% to 5.3%
in the general population, with women experiencing
more severe symptoms. This syndrome typically occurs
in middle-aged adults, but it can develop in any age
group, including childhood, adolescence, as well as
in the elderly (1). Although the cause of fibromyalgia
is uncertain, central nervous system sensitization is
considered to be its major pathogenesis. External factors
such as infection, trauma, and stress may precipitate
it (1,2). No curative treatment for fibromyalgia is
available thus far. A combination of pharmacological
and nonpharmacological treatments is generally
recommended for adequate symptom relief (1). The US
Food and Drug Administration approved duloxetine
(Cymbalta), milnacipran (Savella), and pregabalin
(Lyrica) for treating fibromyalgia. Duloxetine and
milnacipran help control pain levels by changing
some of the brain neurotransmitters (serotonin and
norepinephrine), whereas pregabalin blocks the
overactivated neurons involved in pain transmission.
Physical exercise and cognitive behavior therapy are the
nonpharmacological options with stronger evidence
of efficacy in fibromyalgia (3,4). Other interventional
approaches with lower levels of evidence include
occipital nerve stimulation, lidocaine infusion, and
hyperbaric oxygen therapy (4).
Low-level laser therapy (LLLT) is an emerging,
noninvasive alternative treatment with some efficacy
in relieving musculoskeletal or neuropathic pain and
improving the quality of life (5-10). The mechanism
is believed to involve photochemical reactions, which
alter cell membrane permeability, increase messenger
RNA buildup, and lead to cell proliferation. The light
emitted during LLLT reacts with cytochrome c oxidase, a
respiratory enzyme in mitochondria, and increases ade-
nosine triphosphate (ATP) production and reduces reac-
tive oxygen species levels; this helps reduce cell inflam-
mation and death (11). Some randomized controlled
trials (RCTs) have investigated the efficacy of LLLT for
fibromyalgia. However, the results have been inconsis-
tent, with small sample sizes. Therefore, we conducted
a comprehensive systematic review and meta-analysis
of the effectiveness of LLLT in fibromyalgia, aiming to
contribute to evidence-based decision-making regard-
www.painphysicianjournal.com 243
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
Several domains were evaluated: allocation generation
and concealment; blinding of patients, personnel, and
outcome assessor; incomplete outcome data (intention-
to-treat or per-protocol); and loss to follow-up rate.
Outcome Assessment
To logically and clearly perform the meta-analysis,
the outcome assessment comprised 2 sections. One sec-
tion pooled data from RCTs comparing LLLT with pla-
cebo to evaluate the benefits of LLLT. The other section
pooled data from RCTs comparing LLLT plus standard-
ized exercise with standardized exercise alone in order
to investigate whether applying the additional laser to
exercise therapies provides more benefits than exercise
alone.
In each section, we evaluated 3 primary outcomes,
namely improvement in the total Fibromyalgia Impact
Questionnaire [FIQ] scores (13), severity of pain, and
number of tender points; and 4 secondary outcomes,
namely improvement in fatigue, stiffness, anxiety, and
depression. The improvement in pain severity was as-
sessed by extracting the score of the subitem “pain”
from FIQ (0-10), using a 5-point Likert scale (0 = none,
1= mild, 2 = moderate, 3 = severe, and 4 = extreme), or
by using a visual analog scale (VAS) in cm. As for the
definition of tender points, points that were reported
by patients as being painful were regarded as tender
points; additional tender points were more rigorously
defined if patients felt pain at pressure less than or equal
to 2.6 kgf/cm2 while subject to an increasing pressure of
0.1 kgf/s via placement of an apparatus perpendicular
to the point to be evaluated (14). Improvements in fa-
tigue, stiffness, anxiety, and depression were assessed
using the subitem score of “fatigue” on the FIQ (0-10)
or on the Likert scoring system for grading, “stiffness”
on the FIQ and “morning stiffness” on the Likert scoring
system, “anxiety” on the FIQ, and “depression” on the
FIQ, respectively. In some cases, depression was assessed
by a psychiatrist according to the Hamilton Depression
Rating Scale (HDRS) (15,16), DSM-IV criteria (17), or the
Beck Depression Inventory (18).
Statistical Analysis
We used RevMan 5.3 (The Nordic Cochrane Center
for The Cochrane Collaboration, Copenhagen, Denmark)
to perform the meta-analysis of the RCTs according to
the PRISMA (Preferred Reporting Items for Systematic
Reviews and Meta-Analysis) guidelines (19). The stan-
dardized mean difference (SMD) was calculated as the
effect size for continuous outcomes. The accuracy of the
result was reported as a 95% confidence interval (CI). P
< 0.05 was considered significant. When necessary, the
means and standard deviations of pretreatment-post-
treatment changes were estimated according to the
reported pretreatment and posttreatment data (20).
Due to possible heterogeneity between each study, the
DerSimonian and Laird random-effects model was used
for calculating a pooled estimate of the mean differ-
ence (21). The I-square test was performed to assess the
heterogeneity among these trials.
Results
Study Selection and Characteristics of
Included Studies
Figure 1 illustrates a flowchart of the study se-
lection process. We initially identified 305 potential
trials but excluded 105 duplicates and 97 ineligible
articles after screening their titles and abstracts. Sub-
sequently, 103 additional reports were excluded as
follows: 55 were on different topics, 14 used different
comparisons, 14 were review articles, 6 were systematic
reviews, 3 were protocols, 1 was a cohort study, and
1 was a case study. Finally, the remaining 9 RCTs were
further analyzed.
The characteristics of these eligible studies (14,22-
29) are summarized in Table 1. These 9 RCTs were pub-
lished between 2002 and 2018, with sample sizes of 20
to 80 patients. The mean participant age ranged from
29 to 52 years; however, an earlier trial in 2002 by Gür
et al (29) did not offer any information on age. Most
RCTs only included women, except that the trial by Gür
et al (28) enrolled some male patients and the trial by
Ruaro et al (24) enrolled one man in the placebo group.
All patients had been diagnosed with fibromyalgia.
For patient diagnosis, 6 RCTs (14,22,24,27-29) used the
American College of Rheumatology’s diagnostic criteria
(30), one (23) used the American Rheumatology Society’s
criteria, and the diagnostic criteria were not mentioned
in 2 RCTs (25,26). Patients continued their usual pharma-
cological therapy in one RCT (22), whereas 3 RCTs did
not mention whether the patients were taking medica-
tion concurrently (24-26), some of the patients in one
RCT continued their regular medication for fibromyalgia
(14), and the remaining 4 claimed that no patients took
analgesic, anti-inflammatory medications or central ner-
vous system drugs during the study period.
Regarding laser parameters, 6 RCTs (23,24,26-29)
used GaAlAs or Ga-AS laser, one (25) used Girlase, one
RCT employed a 9-diode cluster device containing mul-
Pain Physician: May/June 2019: 22:241-254
244 www.painphysicianjournal.com
Fig. 1. Flow chart of the process of study selection.
tiple light sources (LLLT and light-emitting diode [LED])
(22), and the latest RCT used a DMC® Photon Laser III de-
vice (14). Therefore, we performed a subgroup analysis
to differentiate the efficacy of monowavelength LLLT
vs an LLLT/LED combination. Laser wavelength ranged
from 640 to 950 nm and power from approximately
0.9 to 1000 MW. The follow-up period of the 8 RCTs
ranged from 2 to 10 weeks; one RCT further followed
for 6 months. Five studies (24,25,27-29) involving 173
patients evaluated the effectiveness of LLLT by com-
paring with placebo laser. Three RCTs compared LLLT
plus stretching exercise with stretching exercise alone
(14,23,26). One RCT designated patients into 4 groups:
control group, phototherapy group, stretching and
aerobic exercise training group, and phototherapy plus
stretching and aerobic exercise training group (22).
Study Quality
As shown in Table 2, the methodological quality of
9 RCTs was assessed (14,22-29). Five RCTs (14,22,24,28,29)
reported acceptable methods of randomization, but
none described allocation concealment methods. Eight
RCTs (14,22-25,27-29) reported patient blinding by ap-
plying placebo or sham laser treatment; the remaining
RCT (26) did not provide any relevant blinding informa-
tion. Three RCTs by Armagan et al (27), da Silva et al
(22) and Germano (14) blinded outcome assessors; da
Silva et al also blinded the phototherapy programmer.
Eight RCTs used an intention-to-treat analysis without
loss to follow-up. However, 20% of the patients with-
drew from one RCT (26) without reporting the reason,
so per-protocol analysis was used for that study. One
RCT reported higher variability of emitted power and
energy dose of laser (26).
Comparison of LLLT and Placebo LLLT
Primary Outcome (FIQ Score, Pain, and Number of
Tender Points)
The meta-analysis showed significant improve-
ment in FIQ score after monowavelength LLLT than
that after placebo laser treatment (pooled SMD: 1.16;
95% CI, 0.64-1.69; I2 = 47%; Fig. 2). The severity of pain
was also significantly reduced in the monowavelength
LLLT group (pooled SMD: 1.18; 95% CI, 0.82-1.54, I2 =
0%; Fig. 3) compared with the placebo groups. A sig-
nificant decrease in the number of tender points after
monowavelength LLLT was also noted (SMD: 1.01; 95%
Table 1. Characteristics of the selected RCTs.
Study Inclusion
Criteria
No. of
Patients Age (yrs) Intervention Outcomes
Germano
(14), 2018
(Brazil)
Diagnosed with
FM by ACR
criteria
I: 11 (0%)
C: 11 (0%)
I: 39.73 ± 5.25
C: 40.36 ± 7.24
I: functional exercise program (40 to 60 min/
session) associated with active phototherapy
(808 nm, 100 mW, continuous, 4 J, and 142.85
J/cm2 on 17 tender points immediately after
exercise, 40 s/site 3 times/wk) x 8 wks
C: functional exercise program (40 to
60 min/session) associated with placebo
phototherapy (3 times/wk) x 8 wks
FIQ, VAS, no. of tender
points, Beck Depression
Inventory, pain
threshold, functional
performance, muscle
performance (flexibility,
strength)
da Silva (22),
2018 (Brazil)
Diagnosed as
FM by ACR
criteria on FIQ
for > 5 yrs, ≥ 35
y/o women
I: 20 (0% a)
C1: 20 (0%)
C2: 20 (0%)
C3: 20 (0%)
Overall:
40 ± 2
I: Phototherapy (a cluster with 9 diodes-1
super-pulsed infrared 905 nm, 4 LED of 640
nm, 4 LED of 875 nm, 39.3 J & 5 min/point x
10 sites) x 10 wks
C1: Placebo phototherapy x 10 wks
C2: Phototherapy + exerciseb x 10 wks
C3: Placebo phototherapy + exerciseb x 10 wks
FIQ, VAS, fatigue, body
stiffness, no. of tender
points, depression,
anxiety, SF-36;
(10 wks)e
Vayvay
(23), 2016
(Turkey)
Diagnosed with
FM by ARS
criteria, ≥18
y/o, continuous
chronic pain ≥
6 mos
I: 15 (0%)
C1: 15 (0%)
C2: 15 (0%)c
I: 36.4 ± 8.3
C1: 38 ± 8.4
C2: 38 ± 9.9 c
I: Ga-AS Laser (850 nm; 40 mW; 2 J/cm2; 50-
60 Hz, 3 min/painful point on back and head)
+ exercise x 3 wks
C1: Placebo laser + exercised x 3 wks
C2: Kinesiotape on the back for 3 wks +
exercised x 3 wks
FIQ, VAS, SF-36, Beck
Depression Inventory
Anxiety Level (3 wks)
Ruaro (24),
2014 (Brazil)
Diagnosed with
FM by ACR
criteria
I: 10 (0%)
C: 10 (10%)
I: 39.4 (34-45)
C: 43.4 (33-55)
I: GaAlAs laser (670 nm, 20 mW, 4 J/cm2 on
18 tender points, 3 times/wk) x 4 wks
C: Placebo laser x 4 wks
FIQ, McGill Pain
Questionnaire, VAS (4
wks)
Fernández
(25), 2011
(Spain)
Diagnosis of FM
for 3-10 yrs, 36-
61 y/o woman
I: 16 (0%)
C: 15 (0%)
I: 51.6 ± 6.18
C: 52.4 ± 5.88
I: Girlase E1.1010 (905 + 10 nm, 0.70 mJ/
drive, 1000 mW boost of the drives, pulsed, 1
min/frequency x 6 on 7 points) x 8 wks
C: Placebo laser x 8 wks
CRD (FIQ), Generalized
pain, fatigue (8 wks)
Matsutani
(26), 2007
(Brazil)
Diagnosed as
FM for 25-60
y/o, exclude
neoplasia
I: 10 (0%)
C: 10 (0%)
I: 44 (28-60)
C: 45 (31-57)
I: GaAlAs laser (830 nm, 3 J/m2, average 30
mW, continuous) + exercised 1 h BIW x 5 wks
C: Placebo laser + exercised 1 h BIW x 5 wks
FIQ, VAS, SF-36 (5 wks)
Amargan
(27), 2006
(Turkey)
Diagnosed with
FM by ACR
criteria
I: 16 (10%)
C: 16 (0%)
I: 38.9 ± 4.9
C: 37.6 ± 5.9
I: GaAlAs laser (830 nm, 50 mW, continuous,
1 min & 2 J/tender point), 5 days/wk x 2 wks
C: Placebo laser 5 days/wk x 2 wks
FIQ, no. of tender
points, morning
stiffness, VSGI
(2 wks)
Gür (28),
2002
(Turkey)
Diagnosed with
FM by ACR
criteria; exclude
major clinical
conditions other
than FM
I: 25 (20%)
C1: 25 (24%)
C2: 25 (16%)c
I: 30.4 ± 6.9
C1: 28.5 ± 6.3
C2: 30.1 ± 8.7c
I: Ga-As laser (904 nm, average 11.2 mW,
2 J/cm2, 2.8 kHz) 3 min/tender point every
afternoon x 2 wks (except weekend)
C1: Placebo laser x 2 wks
C2: Amitriptyline 10 mg at bedtime x 8 wksc
FIQ, depression (HDRS,
DSM-IV), pain, no.
of tender points,
morning stiffness, sleep
disturbance, fatigue (2
wks/6 mos)
Gür (29),
2002 (earlier
published)
(Turkey)
Diagnosed with
FM by ACR
criteria; exclude
major clinical
conditions other
than FM
I: 20 (0%)
C: 20 (0%)
Not mentioned I: Ga-As laser (904 nm, average 11.2 mW,
2 J/cm2, 2.8 kHz) 3 min/tender point every
afternoon x 2 wks (except weekends)
C: Placebo laser x 2 wks
Pain, morning stiffness,
no. of tender points,
sleep disturbance,
fatigue (2 wks)
Abbreviations: ACR, American College of Rheumatology; ARS, American Rheumatology Society; C, Control group; CRD, Cuaderno de re-
cogida de datos; FIQ, Fibromyalgia Impact Questionnaire; FM, Fibromyalgia; HDRS, Hamilton Depression Rating Scale; I, Intervention group;
LED, light-emitting diode; SF-36, 36-item Short-Form Health Survey; VAS, Visual Analog Scale of pain; VSGI, global improvement as reported
on a verbal scale. Age was presented as mean ± SD or mean (range). a (): % men; b stretching and aerobic exercise; c not included for our analy-
sis; d stretching; e (): duration of outcome follow-up
www.painphysicianjournal.com 245
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
Table 2. Methodological quality assessment of the selected RCTs.
Study Allocation
Generation
Allocation
Concealment Blinding Data
Analysis
Loss to
Follow-up
Patient
Gender Other Relevant Remarks
Germano
(14), 2018
Adequate Unclear Patients,
evaluators
ITT 0% Only women Some patients continued regular
medications for fibromyalgia in
2 groups
da Silva (22),
2018
Adequate Unclear Patients,
phototherapy
programmer,
and outcome
assessor
ITT 0% Only women Age distribution not reported;
unknown pharmacological
therapy for fibromyalgia in 2
groups
Vayvay (23),
2016
Unclear Unclear Patients ITT 0% Only women -
Ruaro (24),
2014
Adequate Unclear Patients ITT 0% Only women,
with one man
in the placebo
group
Unknown pharmacological
therapy for fibromyalgia in 2
groups
Fernández
(25), 2011
Unclear Unclear Patients ITT 0% Only women Unknown pharmacological
therapy for fibromyalgia in 2
groups
Matsutani
(26), 2007
Unclear Unclear Unclear PP 20% Only women Unclear reasons for, and
unknown distribution of, loss
of follow-up; may have high
variability of emitted power
and energy dose; unknown
pharmacological therapy for
fibromyalgia in 2 groups
Armagan
(27), 2006
Unclear Unclear Patients and
evaluators
ITT 0% Only women -
Gür (28),
2002
Adequate Unclear Patients ITT 0% - -
Gür (29),
2002 (earlier
published)
Adequate Unclear Patients ITT 0% Only women Age distribution not reported
Abbreviations: ITT, intention to treat; PP, per-protocol; RCT, randomized controlled trial.
Pain Physician: May/June 2019: 22:241-254
246 www.painphysicianjournal.com
Fig. 2. Forest plot of changes in FIQ score after LLLT or placebo laser treatment.
Fig. 3. Forest plot of changes in pain severity after LLLT or placebo laser treatment.
Fig. 4. Forest plot of changes in number of tender points after LLLT or placebo laser treatment.
www.painphysicianjournal.com 247
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
CI, 0.49-1.52; I2 = 49%; Fig. 4). As for the combined LLLT/
LED phototherapy, the only RCT evaluating efficacy
showed significant improvement in FIQ, pain, and num-
ber of tender points compared with the placebo group.
The effect of combined LLLT/LED phototherapy on pain
relief and reduction in the number of tender points
seemed to be more obvious than monowavelength
LLLT (Figs. 3 and 4).
Secondary Outcomes (Fatigue, Stiffness,
Depression, and Anxiety)
In the monowavelength LLLT group, our analysis
showed significant improvements in the severity of
fatigue (pooled SMD: 1.4; 95% CI, 0.96-1.8), stiffness
(pooled SMD: 0.92, 95% CI: 0.36-1.48), depression
(pooled SMD: 1.46, 95% CI: 0.93-2.00), and anxiety
(pooled SMD: 1.46, 95% CI, 0.45-2.47). On the other
hand, the only one RCT evaluating the efficacy of the
combined LLLT/LED phototherapy demonstrated signif-
icant improvement in the severity of fatigue, stiffness,
and anxiety, but not depression, when compared with
those in the placebo laser group.
Comparison of LLLT Plus Exercise and Placebo
Laser Treatment Plus Exercise
Three RCTs evaluated the efficacy of monowave-
length LLLT with exercise (14,23,26). There was no
significant difference between the monowavelength
Pain Physician: May/June 2019: 22:241-254
248 www.painphysicianjournal.com
Fig. 5. Forest plot of changes in severity of fatigue after LLLT or placebo laser treatment.
Fig. 6. Forest plot of changes in severity of stiffness difference after LLLT or placebo laser treatment.
Fig. 7. Forest plot of changes in severity of depression after LLLT or placebo laser treatment.
Fig. 9. Forest plot of changes in FIQ scores between LLLT with exercise and exercise alone.
www.painphysicianjournal.com 249
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
Fig. 8. Forest plot of changes in severity of anxiety after LLLT or placebo laser treatment.
LLLT plus standardized exercise program and exercise
program alone in the primary outcomes of FIQ score
(pooled SMD: 0.34; 95% CI, -0.17 to 0.85; I² = 14%; Fig.
9), pain (pooled SMD: 0.46; 95% CI, -0.10 to 1.01; I² =
0%; Fig. 10) and number of tender points (pooled SMD:
0.59; 95% CI, -0.26 to 1.45; Fig. 11) and secondary out-
comes of fatigue, stiffness, anxiety, or depression (SMD:
-0.16; 95% CI, -1.04 to 0.72; SMD: 0.08; 95% CI, -0.79 to
0.96; SMD: 0.09; 95% CI, -0.80 to 0.98; I² = 70%; SMD:
-0.38; 95% CI, 1.27-0.50, respectively; Figs. 12-15).
Compared with standardized exercise alone, LLLT/
LED combination phototherapy plus exercise program,
as reported in only one RCT, provided significant ad-
ditional benefit in relieving the primary outcome
of the severity of pain and number of tender points
(SMD: 5.20; 95% CI, 3.85-6.55 and SMD: 7.02; 95% CI,
5.29-8.76, respectively) and the secondary outcome of
fatigue (SMD: 1.35; 95% CI, 0.65-2.04), but it not de-
crease in FIQ score, severity of stiffness, or psychiatric
symptoms (Figs. 9-15) (22).
Side Effects
Four RCTs (22,24,27,29) reported no side effects
of LLLT in patients with fibromyalgia, consistent with
previous studies (6,10,31). However, the remaining RCTs
did not report on side effects (14,23,25,26,28).
discussion
LLLT has been introduced as a noninvasive, thera-
peutic intervention for pain in several musculoskeletal
disorders. Some mechanisms, such as increased nocicep-
tive threshold, endorphin production, and downstream
Pain Physician: May/June 2019: 22:241-254
250 www.painphysicianjournal.com
Fig. 12. Forest plot of changes in severity of fatigue between LLLT with exercise and exercise alone.
Fig. 11. Forest plot of changes in number of tender points between LLLT with exercise and exercise alone.
Fig. 10. Forest plot of changes in severity of pain between LLLT with exercise and exercise alone.
www.painphysicianjournal.com 251
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
Fig. 13. Forest plot of stiffness between laser with physical activity and physical activity only.
Fig. 14. Forest plot of depression between laser with physical activity and physical activity only.
Fig. 15. Forest plot of anxiety between laser with physical activity and physical activity only.
Pain Physician: May/June 2019: 22:241-254
252 www.painphysicianjournal.com
opioid receptors, have been postulated to explain the
analgesic effect of phototherapy (32). Other hypoth-
eses include anti-inflammation due to a decrease in
prostaglandin-2 and cyclooxygenase-2 levels (28,32),
proliferation and neovascularization of connective tis-
sue cells (33,34), and increase in blood flow and promo-
tion of healing by increase in the levels of nitric oxide,
a powerful vasodilator (32). A recent systematic review
and meta-analysis of 18 studies suggested that LLLT
effectively reduces pain in adult patients with musculo-
skeletal disorders; however, patients with fibromyalgia
were not included in this meta-analysis (7). Further-
more, studies have indicated the beneficial role of LLLT/
LED combination in the treatment of nonspecific knee
pain (35) as well as masseter and temporalis muscle
pain in women with temporomandibular disorder (36).
Pain is the main symptom in patients with fibromy-
algia. Some RCTs have investigated the effect of LLLT
on fibromyalgia, but by using small sample sizes. Our
study is the first systematic review and meta-analysis
including 9 RCTs involving 325 patients to specifically
evaluate the efficacy of LLLT in fibromyalgia. Our
results demonstrated that LLLT provided significant
improvement in FIQ score, pain severity, number of ten-
der points, fatigue, stiffness, depression, and anxiety
compared to placebo. However, when compared with
pure exercise therapy, LLLT with exercise therapy did
not show more benefits. On the other hand, the single
RCT using LLLT/LED showed significant improvement in
the above-mentioned outcomes, except for depression,
when compared to placebo. When compared with pa-
tients with fibromyalgia who received exercise therapy,
combined LLLT/LED phototherapy and exercise therapy
had additional benefits in reducing the severity of pain,
number of tender points, and fatigue.
However, this review still has some limitations,
mostly because of the low-to-middle methodological
quality of the selected studies (Table 2). First, most stud-
ies did not report the allocation process clearly and only
blinded the patients; neither phototherapy program-
mer nor outcome assessor were blinded. Considering
that nearly all outcomes were subjective parameters,
the above shortcomings may introduce allocation bias,
performance bias, and detection bias. Second, one
study used per-protocol analysis because of a 20% loss
to follow-up without reporting the reasons for, or the
distribution of, the loss to follow-up (26); this may have
introduced attrition bias. Third, although LLLT was used
in all trials, the differences in laser types, energy sourc-
es, and exposure times used in the studies may have
resulted in some heterogeneity. Fourth, although pa-
tients with fibromyalgia did not take associated medi-
cations in most RCTs, patients in one trial maintained
their usual pharmacological therapies (22), another
trial included some patients continuing their regular
medications (14), and the other 3 RCTs did not men-
tion whether the participants were under concurrent
medication (24-26); therefore, we could not clarify the
separate roles of medication or phototherapy in fibro-
myalgia. Finally, long-term follow-up up to 6 months
was only conducted in one RCT (27).
In spite of the limitations, our study is the largest
systematic review and meta-analysis to evaluate the
efficacy of LLLT in patients with fibromyalgia, and it
has provided the most relevant available evidence on
LLLT for fibromyalgia. In conclusion, our data indicate
that LLLT is an emerging, noninvasive, well-tolerated
treatment for fibromyalgia to relieve discomfort, par-
ticularly in patients who do not exercise regularly.
Acknowledgments
We are grateful to Mariana Moreira da Silva and
all her coworkers for providing us with the raw data
of their original study “Randomized, blinded, con-
trolled trial on the effectiveness of photobiomodula-
tion therapy and exercise training in the fibromyalgia
treatment.” This enriched the content of our meta-
analysis and enhanced the power of evidence of LLLT.
This manuscript was edited by Wallace Academic
Editing.
www.painphysicianjournal.com 253
Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis
RefeRences
1. Clauw DJ. Fibromyalgia: A clinical re-
view. JAMA 2014; 311:1547-1555.
2. Watson NF, Buchwald D, Goldberg J,
Noonan C, Ellenbogen RG. Neurologic
signs and symptoms in fibromyalgia.
Arthritis Rheum 2009; 60:2839-2844.
3. Goldenberg DL, Burckhardt C, Crofford
L. Management of fibromyalgia syn-
drome. JAMA 2004; 292:2388-2395.
4. Okifuji A, Gao J, Bokat C, Hare BD.
Management of fibromyalgia syndrome
in 2016. Pain Manag 2016; 6:383-400.
5. de Andrade AL, Bossini PS, Parizotto
NA. Use of low level laser therapy to
control neuropathic pain: A systematic
review. J Photochem Photobiol B 2016;
164:36-42.
6. Glazov G, Yelland M, Emery J. Low-level
laser therapy for chronic non-specific
low back pain: A meta-analysis of ran-
domised controlled trials. Acupunct Med
2016; 34:328-341.
7. Clijsen R, Brunner A, Barbero M, Clarys
P, Taeymans J. Effects of low-level laser
therapy on pain in patients with muscu-
loskeletal disorders: A systematic review
and meta-analysis. Eur J Phys Rehabil
Med 2017; 53:603-610.
8. Deana NF, Zaror C, Sandoval P, Alves N.
Effectiveness of low-level laser therapy
in reducing orthodontic pain: A system-
atic review and meta-analysis. Pain Res
Manag 2017; 2017:8560652.
9. Huisstede BM, Hoogvliet P, Franke TP,
Randsdorp MS, Koes BW. Carpal tun-
nel syndrome: Effectiveness of physical
therapy and electrophysical modalities.
An updated systematic review of ran-
domized controlled trials. Arch Phys Med
Rehabil 2017; 99:1623-1634.
10. Rayegani SM, Raeissadat SA, Heidari S,
Moradi-Joo M. Safety and effectiveness
of low-level laser therapy in patients
with knee osteoarthritis: A systematic
review and meta-analysis. J Lasers Med
Sci 2017; 8:S12-S19.
11. Prindeze NJ, Moffatt LT, Shupp JW.
Mechanisms of action for light therapy:
A review of molecular interactions. Exp
Biol Med (Maywood) 2012; 237:1241-1248.
12. Higgins JP, Altman DG, Gotzsche PC,
Juni P, Moher D, Oxman AD, Savovic J,
Schulz KF, Weeks L, Sterne JA; Cochrane
Bias Methods Group, Cochrane Sta-
tistical Methods Group. The Cochrane
Collaboration’s tool for assessing risk
of bias in randomised trials. BMJ 2011;
343:d5928.
13. Burckhardt CS, Clark SR, Bennett RM.
The fibromyalgia impact questionnaire:
Development and validation. J Rheuma-
tol 1991; 18:728-733.
14. Germano Maciel D, Trajano da Silva M,
Rodrigues JA, Viana Neto JB, de Franca
IM, Melo ABM, Barros da Silva TYP, de
Brito Vieira WH. Low-level laser thera-
py combined to functional exercise on
treatment of fibromyalgia: A double-
blind randomized clinical trial. Lasers
Med Sci 2018; 33:1949-1959.
15. Hamilton M. A rating scale for depres-
sion. J Neurol Neurosurg Psychiatry 1960;
23:56-62.
16. Sharp R. The Hamilton Rating Scale
for Depression. Occup Med (Lond) 2015;
65:340.
17. Bell CC. DSM-IV: Diagnostic and Statis-
tical Manual of Mental Disorders. JAMA
1994; 272:828-829.
18. Beck AT, Ward CH, Mendelson M, Mock
J, Erbaugh J. An inventory for measur-
ing depression. Arch Gen Psychiatry 1961;
4:561-571.
19. Liberati A, Altman DG, Tetzlaff J, Mulrow
C, Gotzsche PC, Ioannidis JP, Clarke M,
Devereaux PJ, Kleijnen J, Moher D. The
PRISMA statement for reporting system-
atic reviews and meta-analyses of studies
that evaluate health care interventions:
Explanation and elaboration. J Clin Epi-
demiol 2009; 62:e1-e34.
20. Hozo SP, Djulbegovic B, Hozo I. Esti-
mating the mean and variance from the
median, range, and the size of a sample.
BMC Med Res Methodol 2005; 5:13.
21. DerSimonian R, Laird N. Meta-analysis
in clinical trials revisited. Contemp Clin
Trials 2015; 45:139-145.
22. da Silva MM, Albertini R, de Tarso Ca-
millo de Carvalho P, Leal-Junior ECP,
Bussadori SK, Vieira SS, Bocalini DS,
de Oliveira LVF, Grandinetti V, Silva JA
Jr, Serra AJ. Randomized, blinded, con-
trolled trial on effectiveness of photobio-
modulation therapy and exercise train-
ing in the fibromyalgia treatment. Lasers
Med Sci 2018; 33:343-351.
23. Vayvay ES, Tok D, Turgut E, Tunay VB.
The effect of Laser and taping on pain,
functional status and quality of life in
patients with fibromyalgia syndrome: A
placebo- randomized controlled clinical
trial. J Back Musculoskelet Rehabil 2016;
29:77-83.
24. Ruaro JA, Frez AR, Ruaro MB, Nico-
lau RA. Low-level laser therapy to treat
fibromyalgia. Lasers Med Sci 2014;
29:1815-1819.
25. Fernandez Garcia R, Suarez Holgado JD,
Formieles Ortiz I, Zurita Ortega F, Val-
verde Cepeda M, Fernandez Sanchez M.
[Using a laser based program in patients
diagnosed with fibromyalgia]. Reumatol
Clin 2011; 7:94-97.
26. Matsutani LA, Marques AP, Ferreira
EA, Assumpcao A, Lage LV, Casarotto
RA, Pereira CA. Effectiveness of muscle
stretching exercises with and without la-
ser therapy at tender points for patients
with fibromyalgia. Clin Exp Rheumatol
2007; 25:410-415.
27. Armagan O, Tascioglu F, Ekim A, Oner
C. Long-term efficacy of low level laser
therapy in women with fibromyalgia: A
placebo-controlled study. J Back Muscu-
loskelet Rehabil 2006; 19:135-140.
28. Gur A, Karakoc M, Nas K, Cevik R, Sarac
J, Ataoglu S. Effects of low power laser
and low dose amitriptyline therapy on
clinical symptoms and quality of life in
fibromyalgia: A single-blind, placebo-
controlled trial. Rheumatol Int 2002;
22:188-193.
29. Gur A, Karakoc M, Nas K, Cevik R, Sarac
J, Demir E. Efficacy of low power laser
therapy in fibromyalgia: A single-blind,
placebo-controlled trial. Lasers Med Sci
2002; 17:57-61.
30. Wolfe F, Clauw DJ, Fitzcharles MA,
Goldenberg DL, Katz RS, Mease P, Rus-
sell AS, Russell IJ, Winfield JB, Yunus
MB. The American College of Rheu-
matology preliminary diagnostic crite-
ria for fibromyalgia and measurement
of symptom severity. Arthritis Care Res
(Hoboken) 2010; 62:600-610.
31. Chow RT, Johnson MI, Lopes-Martins
RA, Bjordal JM. Efficacy of low-level la-
ser therapy in the management of neck
pain: A systematic review and meta-
analysis of randomised placebo or ac-
tive-treatment controlled trials. Lancet
2009; 374:1897-1908.
32. Kingsley JD, Demchak T, Mathis R. Low-
level laser therapy as a treatment for
chronic pain. Front Physiol 2014; 5:306.
33. Bayat M, Virdi A, Rezaei F, Chien S.
Comparison of the in vitro effects of
low-level laser therapy and low-intensity
pulsed ultrasound therapy on bony cells
and stem cells. Prog Biophys Mol Biol
2018; 133:36-48.
Pain Physician: May/June 2019: 22:241-254
254 www.painphysicianjournal.com
34. Chen MH, Huang YC, Sun JS, Chao YH,
Chen MH. Second messengers mediat-
ing the proliferation and collagen syn-
thesis of tenocytes induced by low-level
laser irradiation. Lasers Med Sci 2015;
30:263-272.
35. Leal-Junior EC, Johnson DS, Saltmarche
A, Demchak T. Adjunctive use of combi-
nation of super-pulsed laser and light-
emitting diodes phototherapy on non-
specific knee pain: Double-blinded ran-
domized placebo-controlled trial. Lasers
Med Sci 2014; 29:1839-1847.
36. Herpich CM, Leal-Junior ECP, Gomes C,
Gloria I, Amaral AP, Amaral M, Politti F,
Biasotto-Gonzalez DA. Immediate and
short-term effects of phototherapy on
pain, muscle activity, and joint mobil-
ity in women with temporomandibular
disorder: A randomized, double-blind,
placebo-controlled, clinical trial. Disabil
Rehabil 2018; 40:2318-2324.
... Thus, a multifactorial and definitive treatment is currently lacking. 2,5,6 Photobiomodulation (PBM) therapy, formerly known as low-level laser therapy (LLLT), is an emerging, noninvasive and promising therapy for those suffering from FMS because it has shown positive impact on relieving musculoskeletal and neuropathic pain, with consequent improvement on quality of life. 6 Current research has established effective wavelengths of light used for PBM to range from 600 to 1070 nm, with a fluence (energy density) range of between 1 and 20 J/cm 2 . ...
... 2,5,6 Photobiomodulation (PBM) therapy, formerly known as low-level laser therapy (LLLT), is an emerging, noninvasive and promising therapy for those suffering from FMS because it has shown positive impact on relieving musculoskeletal and neuropathic pain, with consequent improvement on quality of life. 6 Current research has established effective wavelengths of light used for PBM to range from 600 to 1070 nm, with a fluence (energy density) range of between 1 and 20 J/cm 2 . Effective tissue penetration is maximised in this range, as the principal tissue chromophores (haemoglobin and melanin) have high absorption bands at wavelengths shorter than 600 nm. ...
... [7][8][9] Previous studies have shown positive effects of PBM in patients suffering from FMS, such as a decrease in pain, sleep disorders, tiredness, muscle spasm, morning stiffness and tender point numbers. 6,[10][11][12] Recently, the possibility of a whole-body PBM has been shown, offering not only a local but also a systemic response. In this regard, improvements in neuronal bioenergetic functions, cerebral blood flow, oxidative stress, neuroinflammation, neural apoptosis, neurotrophic factors, neurogenesis and effects on intrinsic brain networks have been proposed, thus including a brain PBM treatment. ...
Article
Full-text available
Background The development of an integral and global treatment to improve the quality of life in those with fibromyalgia syndrome (FMS) is challenging. The aim of this study is to investigate the impact of whole-body photobiomodulation (PBM) on pain perception, functionality, quality of soft tissue, central sensitisation and psychological factors in patients suffering with FMS. Methods This study is a randomised, placebo-controlled clinical trial. A total of 44 participants will be recruited in a private care practice and randomised to receive either a whole-body PBM therapy programme or placebo in the same care centre. The parameters of the PBM programme are as follows: wavelengths of red and near-infrared LEDs 50:50 ratio with 660–850 nanometers; fluence of 25.2 J/cm ² ; treatment time of 1200 s and a total power emitted of 967 W. Treatment sessions will be 3 times weekly for a period of 4 weeks, totalling 12 treatment sessions. Primary outcome will be pain (Numeric Pain Rating Scale; Widespread Pain Index; Symptom Severity Score). Secondary outcomes will be functionality (Fibromyalgia Impact Questionnaire; the Leisure Time Physical Activity Instrument), quality of soft tissue (elastography), central sensitisation (pain pressure threshold and the Autonomic Symptom Profile) and psychological factors (Pain Catastrophising scale, Tampa Scale, Self-Efficacy questionnaire). Assessments will be at baseline (T1), after session 6 (T2), after treatment (T3) and 2 weeks (T4), 3 (T5) and 6 (T6) month follow-up. Discussion PBM therapy has been shown to reduce pain and inflammation and to increase the rate of tissue repair for a wide range of conditions, but its potential use as a whole-body treatment in FM is yet to be explored. This trial will investigate whether whole-body PBM therapy is effective at reducing pain intensity, improving functionality, quality of soft tissue, central sensitisation symptoms and psychological measurements. Furthermore, 3- and 6-month follow-up will investigate long-term efficacy of this treatment. Trial registration NCT04248972. Registered on January 29, 2020, https://clinicaltrials.gov/ct2/show/NCT04248972?term=navarro-ledesma+santiago&draw=2&rank=2 .
... Despite some physical therapy interventions, such as exercise and cognitive behavior therapy showing some therapeutic bene t [2][3][4], FMS is a complex syndrome and there is little evidence to con rm if the condition is fully improved in all aspects using these treatment programs. Thus a multifactorial and de nitive treatment is currently lacking [2,4,5]. Photobiomodulation (PBM) therapy, formerly known as Low-level laser therapy (LLLT), is an emerging, non invasive and promising therapy for those suffering from FMS, since it has shown positive impact on relieving musculoskeletal and neuropathic pain, with consequent improvement on quality of life [5].Current research has established effective wave lengths of light used for PBM to range from 600 to 1070 nm, with a uence (energy density) range of between 1 and 20 J/cm 2 . ...
... Thus a multifactorial and de nitive treatment is currently lacking [2,4,5]. Photobiomodulation (PBM) therapy, formerly known as Low-level laser therapy (LLLT), is an emerging, non invasive and promising therapy for those suffering from FMS, since it has shown positive impact on relieving musculoskeletal and neuropathic pain, with consequent improvement on quality of life [5].Current research has established effective wave lengths of light used for PBM to range from 600 to 1070 nm, with a uence (energy density) range of between 1 and 20 J/cm 2 . Effective tissue penetration is maximised in this range, as the principal tissue chromophores (haemoglobin and melanin) have high absorption bands at wave lengths shorter than 600 nm. ...
... Therefore, they may show a lack of energy in response to any physical activity[8, 33,34]. This allows an increase in sensitisation of the whole body over time, leading to chronicity of pain and tenderness of soft tissue in those with FMS [5,8,9]. Similarly, chronic pain is associated with fatigue as well as having psychologicali mpact [34]. ...
Preprint
Full-text available
Background: The development of an integral and global treatment to improve the quality of life in those with fibromyalgia syndrome (FMS) is challenging. Methods: This study is a randomized, placebo-controlled clinical trial. Participants will be recruited in a private care practice and randomized to receive either a whole body Photobiomodulation (PBM) therapy program or placebo. Primary out comes will be pain (NumericPain Rating Scale; Widespread Pain Index; Symptom Severity Score), functionality (Fibromyalgia Impact Questionnaire; The Leisure Time Physical Activity Instrument), quality of soft tissue (elastography) and central sensitisation (pain pressure threshold and the Autonomic Symptom Profile). Secondary outcomes will be psychological factors (Pain Catastrophising scale, Tampa Scale, Self-Efficay questionnaire). Assessments will be at baseline (T1), after session 6 (T2), after treatment (T3) and 2 weeks (T4), 3 (T5) and 6 (T6) month´ follow-up. Discussion: PBM therapy has been shown to reduce pain and inflammation and to increase the rate of tissue repair for a wide range of conditions, but its potential use as a whole body treatment in FM is yet to be explored. This trial will investigate whether whole body PBM therapy is effective at reducing pain intensity, improving functionality, quality of soft tissue, central sensitisation symptoms and psychological measurements. Furthermore, 3 and 6 months follow up will investigate long-term efficacy of this treatment. Trial registration: NCT04248972. Registered on January 29, 2020, https://clinicaltrials.gov/ct2/show/NCT04248972?term=navarro-ledesma+santiago&draw=2&rank=2.
... In recent years, LILT has been explored as a treatment option for fibromyalgia, plantar fasciitis, Achilles tendinopathy, myofascial neck pain, and Bouchard's and Heberden's osteoarthritis [23][24][25][26][27][28][29]. In regards to fibromyalgia, Yeh et al.'s 2019 systematic review and meta-analysis of 9 RCTs found that LILT improved patient Fibromyalgia Impact Questionnaire (FIQ) scores, pain severity, number of tender points, stiffness, depression, and anxiety compared to placebo laser [23]. ...
... In recent years, LILT has been explored as a treatment option for fibromyalgia, plantar fasciitis, Achilles tendinopathy, myofascial neck pain, and Bouchard's and Heberden's osteoarthritis [23][24][25][26][27][28][29]. In regards to fibromyalgia, Yeh et al.'s 2019 systematic review and meta-analysis of 9 RCTs found that LILT improved patient Fibromyalgia Impact Questionnaire (FIQ) scores, pain severity, number of tender points, stiffness, depression, and anxiety compared to placebo laser [23]. Similar improvements were seen in LILT's ability to relieve chronic foot and ankle joint pain, although range of motion (ROM) remained unimproved [29]. ...
Article
Full-text available
Purpose of Review Chronic pain management therapies have expanded quickly over the past decade. In particular, the use of laser therapy and ultrasound in the management of chronic pain has risen in recent years. Understanding the uses of these types of therapies can better equip chronic pain specialists for managing complicated chronic pain syndromes. The purpose of this review was to summarize the current literature regarding laser radiation and ultrasound therapy used for managing chronic pain syndromes. Recent Findings In summary, there is stronger evidence supporting the usage of laser therapy for managing chronic pain states compared to low-intensity ultrasound therapies. As a monotherapy, laser therapy has proven to be beneficial in managing chronic pain in patients with a variety of pain syndromes. On the other hand, LIUS has less clear benefits as a monotherapy with an uncertain, optimal delivery method established. Summary Both laser therapy and low-intensity ultrasound have proven beneficial in managing various pain syndromes and can be effective interventions, in particular, when utilized in combination therapy.
... Photobiomodulation (PBM), previously referred to as low-level laser therapy, is a form of near-infrared (NIR) light therapy shown in several systematic reviews to improve pain in musculoskeletal and arthritic conditions such as low back pain, fibromyalgia, knee and shoulder pain [11][12][13]. The NIR light triggers biochemical changes within cells, where the photons are absorbed by chromophores and initiate a chain of intracellular chemical reactions [14]. ...
... Although PBM has been shown to be an effective treatment for a variety of musculoskeletal and arthritic chronic pain conditions [11][12][13], to our knowledge, this is the first study evaluating PBM for the treatment of CPP. In this cohort, more than 90% of women who tried one treatment continued beyond three treatments. ...
Article
Aim: This research is the first to evaluate the effectiveness of trans-vaginal photobiomodulation therapy (TV-PBMT) for chronic pelvic pain. Materials & methods: Observational analysis of 128 women, undergoing TV-PBMT for chronic pelvic pain. Minimal Clinically Important Difference, defined as ≥2-point drop on a 0–10 numeric pain rating scale (NPRS), and effect size Cohen d coefficient, was calculated over nine treatments for overall pain, and pain with activities. Results: Compared with baseline, 64.5% of women showed improvement in overall pain, pain with bowel movement, intercourse, exercise, urination, sitting and vulvar pain (Minimal Clinically Important Difference = -2.4, -2.0, -2.4, -2.1, -2.1, -2.0, -3.1; d = 0.9, 0.7, 0.9, 0.7, 0.7, 0.7, 0.9) by treatment 9. Conclusion: In this cohort, TV-PBMT resulted in improvement of pelvic pain without serious adverse events.
... Open access primary evaluation that focuses on descriptive analysis of feasibility/process outcomes (eg, recruitment, adherence and treatment fidelity). 36 In order to gauge our sample size, we took data from a 2019 meta-analysis on focused PBM therapy in fibromyalgia, 45 as best proxy of the widespread chronic pain and included all of the symptoms under observation in this study. Our chosen sample size takes into account the study population's number of visits at our clinics, objectives of the study and recommendations for the sample size calculations in pilot and feasibility trials by Moore et al 46 Lancaster and Thabane, 47 Lewis et al 48 as well as the 'rules of thumb' for feasibility trials as set out by Kieser and Wassmer. ...
Article
Full-text available
Introduction Chronic pain conditions are a leading cause of disease and disability. They are associated with symptoms such as fatigue, sleep and mood disturbances. Minimal evidence is available to support effective treatments and alternatives treatment approaches are called for. Photobiomodulation therapy has been highlighted as one promising option. A whole-body therapy device (NovoTHOR) has recently been developed with a number of potential advantages for people with chronic pain. Research is needed to consider the feasibility of this device. Methods and analysis A single-centre single-armed (no placebo group) feasibility study with an embedded qualitative component will be conducted. The intervention will comprise 18 treatments over 6 weeks, with 6-month follow up, in the whole-body photobiomodulation device. A non-probability sample of 20 adult participants with a clinician diagnosis of chronic axial pain, polyarthralgia, myofascial pain, or widespread pain will be recruited (self- and clinician referral). Outcome measures will focus on acceptability of trial processes with a view to guiding a definitive randomised controlled trial. Analyses will utilise descriptive statistics for quantitative aspects. The qualitative element will be assessed by means of a participant-reported experience questionnaire post-intervention and semi-structured audio-recorded interviews at 3 stages; pre-, mid- and post-intervention. The latter will be transcribed verbatim and a reflexive thematic analysis will be used to identify emerging themes. Exploratory outcomes (participant-reported and performance-based measures) will be analysed according to data distribution. Ethics and dissemination The study has received ethical approval from the Leicester Central Research and Ethics Committee. Findings will be disseminated via local chronic pain groups, public register update, submission for presentation at scientific meetings and open-access peer-reviewed journals, and via academic social networks.
... 21 Randomized clinical trials and systematic reviews confirm that PBM can safely improve pain and reduce inflammation in musculoskeletal chronic conditions such as low back pain, fibromyalgia, as well as knee and shoulder pain. [22][23][24] Given its effect on myofascial and visceral tissue, we speculated that transvaginal PBM (TV-PBM) may benefit patients with CPP, where inflammation and hypertonic muscular dysfunction contributes to pain. The primary endpoint of this study was to assess the effect of TV-PBM on pain severity in women with CPP. ...
Article
Background: Chronic pelvic pain (CPP) is a common and debilitating condition that affects millions of U.S. women. Most treatments are ineffective and innovative new therapies are desperately needed. Large, controlled studies show that photobiomodulation (PBM) can reduce pain in patients with other chronic pain conditions, such as low back pain, neck pain, and fibromyalgia. The objective of this pilot study was to determine if transvaginal PBM (TV-PBM) can reduce pain in women with CPP. Methods: We conducted a before and after, observational, pilot study. Patients completed the Short Form-McGill Pain Questionnaire (SF-MPQ) at baseline, 1 week, 3 months, and 6 months after nine treatments of TV-PBM. Clinicians completed the Clinical Global Impression Scale (CGI) assessing patient illness severity at the same time. Wilcoxon rank-sum t-tests and effect size using Cohen's d coefficient (low effect size if d < 0.2, medium if 0.2 < d > 8, and high if d > 0.8) was used to measure degree of pain improvement, which was also considered clinically significant if pain reduction was >30%. Results: Thirteen women completed 9 treatments, and 10 women were successfully followed to 6 months. At baseline, the mean SF-MPQ score was 19.7 (standard deviation [SD] ± 5.9). Compared with baseline, 60% improved; the mean SF-MPQ score decreased to 10.0 (SD ±7.5, p = 0.004, d = 1.6) at 1 week after treatment, to 9.7 (SD ±7.9, p = 0.005, d = 1.7) at 3 months, and 8.2 (SD ±8.1, p = 0.002, d = 1.9) at 6 months. Conclusion: Transvaginal PBM provided significant and sustained pain relief to women with CPP up to 6 months. Further controlled studies are needed to confirm these findings, however, in this initial pilot, TV-PBM shows promise.
... The LLLT has the advantages of being a non-invasive procedure and using a low-level laser (usually below 500 mW), thus not causing ablation or increasing tissue temperature, providing safety for clinical use [28]. Studies have shown the efficacy of its application in reducing the side effects of chemotherapy for head and neck cancer [29] and fibromyalgia [30]. ...
Article
Full-text available
The purpose of this study was to systematically review the scientific evidence of the effect of low-level laser therapy (LLLT) on the perception of pain, edema, and trismus after orthognathic surgery. The literature was searched in 11 databases (MedLine via PubMed, Scopus, LILACS, SciELO, Embase, Web of Science, Cochrane Library, and LIVIVO, OpenGrey, OADT, and OpenThesis), without restriction of publication year or language. This search aimed to identify randomized clinical trials comparing low-level laser therapy and placebo for controlling pain, edema, and trismus after orthognathic surgeries. Two reviewers extracted the data and assessed the individual risk of bias of the eligible studies using the Cochrane Collaboration Risk of Bias Tool (RoB, version 2.0). The initial search resulted in 808 articles, from which only five (total of 190 participants) were included in the qualitative synthesis. The studies were published from 2014 to 2020. Two presented a low risk of bias + in the mean mouth opening of all patients subjected to bimaxillary surgery who received LLLT. However, the other study found a significant difference in maximum mouth opening in the LLLT group at 14, 30, and 60 days after surgery. Based on limited evidence, LLLT was presented as an auxiliary tool for reducing pain and trismus after surgery. However, the reduction of edema is controversial due to the absence of measuring standardization.
... [16][17][18][19] Although this red light belonged to "low level laser therapy", also known as Photobiomodulation, For myopia, it could be regarded as an innovative method. For neurological and psychological conditions, [19] stroke, [20] pain relief, [21] fibromyalgia [22] as well as age-related macular degeneration, [23] amblyopia, retinopathy of prematurity, diabetic retinopathy, and Leber's hereditary optic neuropathy, it had already gained the attention of the clinical community as a promising approach. [24] And the reason for shortening axial length of myopia could be caused directly by increasing choroidal thickness, choroidal metabolic rate and circulation to avoid scleral hypoxia. ...
... The major's clinical applications of PBM, focus on wound's tissues and nerves healing and regeneration [26][27][28], treatment of neurological disorders, pain, inflammation, edema relief and chronic joint disorders [29][30][31][32]. ...
Article
Photobiomodulation (PBM) has been applied as a non-invasive technique for treating temporomandibular joint symptoms, especially on painful condition's relief, however the anti-inflammatory mechanism underlying the effect of PBM remains uncertain. This study aims to evaluate the mechanisms of action of PBM (808 nm) in a carrageenan-induced inflammation on temporomandibular joint (TMJ) of rats. In this study male Wistar rats were pre-treated with irradiation of a low-power diode laser for 15 s on TMJ (infra-red 808 nm, 100 mW, 50 J/cm² and 1.5 J) 15 min prior an injection in the temporomandibular joint of carrageenan (100 μg/TMJ). 1 h after the TMJ treatments, the rats were terminally anesthetized for joint cavity wash and periarticular tissues collect. Samples analysis demonstrated that PBM inhibit leukocytes chemotaxis in the TMJ and significantly reduces amounts of TNF-α, IL-1β and CINC-1. In addition, Western blotting analysis demonstrated that PBM significantly decreased the protein levels of P2X3 and P2X7 receptors in the periarticular tissues. On the other hand, PBM was able to increase protein level of IL-10 (anti-inflammatory cytokine). In summary, it is possible to suggest that PBM inhibit inflammatory chemotaxis, modulation the balance of the pro- and anti-inflammatory characteristics of inflammatory cells.
... Favourable results observed in MSD of nonarticular origin are promising and encourage us to con tinue developing new RCTs under these conditions. This is also supported by research conducted with LILT that verifies its use in pain management in myofascial conditions and tendinopathies [50][51][52]. ...
Article
Full-text available
Introduction. Musculoskeletal disorders (MSDs) are the main reason for disability in the world, causing pain and functional loss. Class IV laser is a recent treatment proposed for pain reduction in MSDs, although studies supporting its use and dosage are limited. The purpose of the paper was to describe the efficacy of class IV laser in the treatment of musculoskeletal pain. Methods. Randomized clinical trials were identified in the PubMed, Scopus, Web of Science, CINAHL, and ScienceDirect databases by a search on August 31, 2020. Three independent investigators reviewed article titles and abstracts for eligibility. Risk of bias and quality were evaluated with the Cochrane risk of bias tool and PEDro scale. Decreased pain was considered the main outcome; range of motion, strength, or disability were secondary outcomes. Results. A total of 50 articles were obtained after eliminating duplicates, reduced to 7 after selection criteria application. MSDs included patellofemoral dysfunction (n = 1), epicondylitis (n = 1), osteoarthritis (n = 1), cervicalgia (n = 3), and lumbar radiculopathy (n = 1). The studies had a low risk of bias and a PEDro score greater than 7. Pain reduction was observed at the end of laser treatments and in followup evaluations (p < 0.005); the decrease in disability favoured laser management (p < 0.005). Conclusions. Class IV laser is effective in reducing pain and improving function in patients with MSDs. Further research is necessary to establish a consensus on the dosage and obtain more evidence in MSDs of nonarticular origin.
Article
Full-text available
This study aims to investigate the effects of low-level laser therapy (LLLT) combined to a functional exercise program on treatment of FM. A double-blind and placebo-controlled randomized clinical trial composed of 22 women divided into two groups: placebo group (functional exercise program associated with placebo phototherapy n = 11) and laser group (same exercise program associated with active phototherapy; n = 11). Each session lasted from 40 to 60 min and was performed three times a week for 8 weeks. Phototherapy (808 nm, 100 mW, 4 J, and 142.85 J/cm² per point) was bilaterally applied to different points of the quadriceps (8), hamstrings (6), and triceps sural muscles (3) immediately after each exercise session. Pre- and post-intervention evaluations regarding pain (sites, intensity, and threshold), functional performance (balance, functional tests), muscle performance (flexibility and isokinetic variables), depression, and quality of life were conducted. A reduction in pain and improvement in functional and muscular performance, depression, and quality of life were observed in both groups (p < 0.05); however, with no significant differences between them (p > 0.05). In conclusion, the benefic effects of functional exercise were not improved by combination with LLLT.
Article
Full-text available
This study evaluated the role of the phototherapy and exercise training (EXT) as well as the combined treatment in general symptoms, pain, and quality of life in women suffering from fibromyalgia (FM). A total of 160 women were enrolled and measures were carried out in two sets: it was sought to identify the acute effect for a single phototherapy and EXT session (Set 1); long-term effect (10 weeks) of the interventions (Set 2). Phototherapy irradiation was performed at 11 locations in their bodies, employing a cluster with nine diodes (one super-pulsed infrared 905 nm, four light-emitting diodes [LEDs] of 640 nm, and four LEDs of 875 nm, 39.3 J per location). Algometry and VAS instrument were applied to evaluate pain. The FM symptoms were evaluated with Fibromyalgia Impact Questionnaire (FIQ) and Research Diagnostic Criteria (RDC) instruments. Quality of life was assessed through SF-36 survey. Set 1: pain threshold was improved with the phototherapy, and EXT improved the pain threshold for temporomandibular joint (right and left body side) and occipital site (right body side). Set 2: there was improved pain threshold in several tender points with the phototherapy and EXT. There was an overlap of therapies to reduce the tender point numbers, anxiety, depression, fatigue, sleep, and difficulty sleeping on FIQ/RDC scores. Moreover, quality of life was improved with both therapies. The phototherapy and EXT improved the pain threshold in FM women. A more substantial effect was noticed for the combined therapy, in which pain relief was accomplished by improving VAS and FIQ scores as well as quality of life.
Article
Full-text available
Objectives To assess the effectiveness of low-level laser therapy (LLLT) in reducing orthodontic pain after the application of orthodontic force (OF). Methods A systematic search was conducted in the MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science, and EBSCOhost databases. The study included randomized clinical trials (RCT) which analysed the effectiveness of LLLT in reducing orthodontic pain assessed at 24 and 72 hrs after the application of OF. The risk of bias of the eligible trials was assessed using the Cochrane Collaboration's risk of bias tool. Standard mean difference was calculated and pooled by meta-analysis using random effect models. Results Of 467 identified articles, 20 RCT were finally included. In the risk of bias assessments, 13 studies presented a high risk, 5 an unclear risk, and 2 a low risk. The meta-analysis showed that in patients treated with laser versus placebo there was a difference in favour of LLLT in spontaneous pain 24 and 72 hrs after the installation of light archwires and spontaneous pain and chewing pain 24 and 72 hrs after the installation of elastomeric separators. Conclusions LLLT proved to be effective in promoting a reduction in spontaneous and chewing pain after the application of OF; however, the poor quality of the evidence requires these results to be treated with caution.
Article
Full-text available
Introduction: Low-level laser therapy (LLLT) was introduced as an alternative non-invasive treatment for osteoarthritis, but its effectiveness is still controversial. The main objective of this article was to determine the safety and efficacy of LLLT in patients with knee osteoarthritis (KOA). Methods: In order to gather evidence, main medical databases as well as relevant websites were browsed without time limit. We searched with appropriate keywords and strategies. After quality assessment of studies, study data were extracted by two reviewers. Standard mean difference proposed through inverse variance was used in the meta-analysis using the random-effects model. Twelve values were used for the evaluation of heterogeneity. Results: A total of 823 studies, 14 randomized controlled trials (RCTs) were selected after final review. There was a significant difference between LLLT and placebo in pain at rest (P = 0.02), pain at activity (P = 0.01), total pain (P = 0.03), WOMAC function (P = 0.01), WOMAC stiffness (P = 0.02) and WOMAC total (P < 0.0001) in favor of the LLLT. There was no significant difference between LLLT and Placebo in WOMAC pain (P = 0.09) and range of motion (P = 0.1). Conclusion: In spite of some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected with important factors: wavelength, energy density, treatment duration, numbers of sessions the treatment, severity of KOA and site of application.
Article
Full-text available
Introduction: This meta-analysis investigated the effectiveness of low-level laser therapy (LLLT) on pain in adult patients with musculoskeletal disorders. Evidence acquisition: A systematic literature search was conducted in the Medline and PEDro databases. Two researchers independently screened titles and abstracts of the retrieved studies for eligibility. Quality assessment of the eligible studies was conducted using the PEDro rating scale. Studies that scored ≥ 4 were included. A random-effects model was used for this meta-analysis. Subgroup meta-analyses were conducted to evaluate the influence of the adherence of the applied LLLT to the World Association of Laser Therapy (WALT) guidelines, the anatomical site under investigation and the study design on the overall weighted mean effect size. Meta regression was used to assess the possible influence of the study quality on the individual study effect sizes. Evidence synthesis: Eighteen studies allowing for 21 head-to-head comparisons (totaling n=1462 participants) were included. The pooled raw mean difference (D) in pain between LLLT and the control groups was -0.85 [95%CI: -1.22 to -0.48]. There was high (I² = 85.6%) and significant between study heterogeneity (Cochran's Q = 139.2; df = 20; p < 0.001). The subgroup meta-analysis of the comparisons not following the WALT guidelines revealed a D = -0.68 [95%CI: -1.09 to -0.27]. In this group, heterogeneity decreased to I² = 72.6% (Q = 51.2; df = 14; p < 0.001). In the WALT subgroup D equaled -1.52 [95%CI: -2.34 to -0.70]. this between groups difference was clinically relevant although statistically not significant (Q = 3.24; df = 1; p = 0.072). Conclusions: This meta-analysis presents evidence that LLLT is an effective treatment modality to reduce pain in adult patients with musculoskeletal disorders. Adherence to WALT dosage recommendations seems to enhance treatment effectiveness.
Article
Full-text available
Neuropathic pain can be defined as pain initiated or caused by a primary lesion or dysfunction in the central or peripheral nervous system. The low level laser therapy (LLLT) has gained great prominence as a treatment in this type of pain; however, the application parameters are still controversial in the literature. This study aimed to review the literature on the use of LLLT in neuropathic pain with the goal of establishing a “therapeutic window” for the effective use of this treatment. We analyzed 14 articles, 10 in experimental animals and 4 in humans. The results are presented in three tables, the first being for comparison of the studies' application parameters, the second showing the average and median parameters experimental studies and third showing the clinical studies embodiment. The experimental studies revealed better results for LLLT and infrared laser powers above 70 mW. Clinical studies are inconclusive as to the application parameters, due to the discrepancy; however all demonstrate the effectiveness of LLLT. According to the data presented, it was concluded that LLLT has positive effects on the control of analgesia for neuropathic pain, but further studies with high scientific rigor are needed in order to define treatment protocols that optimize the action LLLT in neuropathic pain.
Article
To compare the in vitro effectiveness of Low-Level Laser Therapy (LLLT) and Low Intensity Pulsed Ultrasound (LIPUS) on bony cells and related stem cells. In this study, we aim to systematically review the published scientific literature which explores the use of LLLT and LIPUS to biostimulate the activity or the proliferation of bony cells or stem cells in vitro. We searched the database PubMed for LLLT or LIPUS, with/without bone, osteoblast, osteocyte, stem cells, the human osteosarcoma cell line (MG63), bone-forming cells, and cell culture (or in vitro). These studies were subdivided into categories exploring the effect of LLLT or LIPUS on bony cells, stem cells, and other related cells. 75 articles were found between 1987 and 2016; these included: 50 full paper articles on LLLT and 25 full papers on LIPUS. These articles met the eligibility criteria and were included in our review. A detailed and concise description of the LLLT and the LIPUS protocols and their individual effects on bony cells or stem cells and their results are presented in five tables. Based on the main results and the conclusions of the reviewed articles in the current work, both, LLLT and LIPUS, apply a biostimulatory effect on osteoblasts, osteocytes, and enhance osteoblast proliferation and differentiation on different bony cell lines used in in vitro studies, and therefore, these may be useful tools for bone regeneration therapy. Moreover, in consideration of future cell therapy protocols, both, LLLT and LIPUS (especially LLLT), enhnce a significant increase in the initial number of SCs before differentiation, thus increasing the number of differentiated cells for tissue engineering, regenerative medicine, and healing. Further studies are necessary to determine the LLLT or the LIPUS parameters, which are optimal for biostimsulating bony cells and SCs for bone healing and regenerative medicine.