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R E S E A R C H Open Access
The effect of low-level red and near-
infrared photobiomodulation on pain and
function in tendinopathy: a systematic
review and meta-analysis of randomized
control trials
Nicholas Tripodi
1,2,3*
, Jack Feehan
1,3,4
, Maja Husaric
1,2
, Fotios Sidiroglou
2,5
and Vasso Apostolopoulos
1
Abstract
Background: Tendinopathy is a common clinical condition that can significantly affect a person’s physical function
and quality of life. Despite exercise therapy being the mainstay of tendinopathy management, there are many
potential adjunct therapies that remain under investigated, one of which is photobiomodulation (PBM). PBM uses
varied wavelengths of light to create a biological effect. While PBM is used frequently in the management of
tendinopathy, high quality evidence supporting its utility is lacking.
Methods: A systematic search of the Pubmed, CINAHL, SCOPUS, Cochrane Database, Web of Science and
SPORTSDICUS databases was performed for eligible articles in August 2020. Randomized Control Trials that used red
or near-infrared PBM to treat tendinopathy disorders that made comparisons with a sham or ‘other’intervention
were included. Pain and function data were extracted from the included studies. The data were synthesized using a
random effects model. The meta-analysis was performed using the mean difference (MD) and standardized mean
difference (SMD) statistics.
Results: A total of 17 trials were included (n= 835). When compared solely to other interventions PBM resulted in
similar decreases in pain (MD -0.09; 95% CI −0.79 to 0.61) and a smaller improvement in function (SMD -0.52; 95%
CI −0.81 to −0.23). When PBM plus exercise was compared to sham treatment plus exercise, PBM demonstrated
greater decreases in pain (MD 1.06; 95% CI 0.57 to 1.55) and improved function (MD 5.65; 95% CI 0.25 to 11.04).
When PBM plus exercise was compared to other interventions plus exercise, no differences were noted in pain
levels (MD 0.31; 95% CI −0.07 to 0.70). Most studies were judged as low-risk of bias. The outcome measures were
classified as very low to moderate evidence quality according to the Grading of Recommendation, Development
and Evaluation tool.
Conclusion: There is very-low-to-moderate quality evidence demonstrating that PBM has utility as a standalone
and/or adjunctive therapy for tendinopathy disorders.
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data made available in this article, unless otherwise stated in a credit line to the data.
* Correspondence: nicholas.Tripodi@vu.edu.au
1
Institute for Health and Sport, Victoria University, Room 1.16, 301 Flinders
Lane, Melbourne, VIC 3000, Australia
2
First Year College, Victoria University, Melbourne, Australia
Full list of author information is available at the end of the article
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91
https://doi.org/10.1186/s13102-021-00306-z
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Trial registration: PROPERO registration number: CRD42020202508.
Keywords: Tendinopathy, Photobiomodulation, Pain, Low-level laser therapy, Meta-analysis, Systematic review
Background
Tendinopathies represent a common presentation to
clinical practice, particularly in active persons [1]. For
instance, Achilles tendinopathy has been reported to
occur at a rate of 2.35 per 1000 patients [2], whilst oc-
curring between 6.2–9.5% in athletic populations [3]. Re-
gardless of cohort, tendinopathy can profoundly affect a
person’s quality of life and ability to perform activities of
daily living, and cause considerable economic impact [4].
Traditionally, tendon pain was known as tendinitis, re-
ferring to the pain and inflammation thought to be asso-
ciated with this condition [4]. However, as research in
this area advanced, it was noted that most painful ten-
don disorders are chronic disorders, lacking a primary
inflammatory driver [5–7]. Hence, the next term that
evolved to describe this disorder was tendinosis, refer-
ring to the deleterious histopathological changes that
can occur within a painful tendon [5]. More contempor-
ary research now advocates for the term tendinopathy
when describing any painful tendon disorder [7,8]. Des-
pite the original definition being grounded in the histo-
pathological and clinical findings [7], tendinopathy is
now defined as persistent tendon pain and loss of func-
tion related to mechanical loading [8], which may be as-
sociated with radiological changes [9].
Despite extensive research efforts in recent years, the
complete pathophysiological picture of tendinopathy re-
mains poorly understood [1]. However, it is known that
four key cellular changes typify tendon pathology: 1. In-
creased number and metabolism of tenocytes; 2. Large pro-
teoglycan presence, causing increased water content; 3.
Abnormal collagen alignment and 4. New blood vessel and
nerve growth within the tendon [10]. Regardless of the
exact pathophysiological mechanisms, diagnosis of tendino-
pathy is primarily clinical, rather than radiological [1]. Ten-
dinopathy presents as localized tendon pain that is
correlated to mechanical load, that is beyond the tendon’s
current capacity [8]. A clinician must pay close attention to
changes in activity load and other rheumatological, meta-
bolic and endocrine risk factors, with pain being produced
during specific provocative movements, or by activities of
daily living [1]. Furthermore, given the poor correlation be-
tween pain, function and histopathological radiological
findings [10], and the absence of a defined nociceptive ten-
dinopathic pathway [1], it is also important to consider the
psychosocial influences of tendinopathy [1,4,11].
Due to the common prevalence of tendinopathy there
is a large variety of treatment methodologies that have
been employed, of which, exercise rehabilitation is the
most well supported [1,12,13]. There are also a number
of adjunct therapies used in the management of tendino-
pathy, including: Extracorporeal shock wave therapy
(ESWT), Non-steroidal anti-inflammatory drugs (NSAI
Ds), injection therapies such as platelet rich plasma
(PRP), corticosteroids (CS), and prolotherapy, transder-
mal application of CS through the method of Iontophor-
esis, and also passive interventions such as stretching
and deep friction massage [1,13]. While some of these
treatments show promise, most have been shown to be
no better, or worse that exercise rehabilitation [1].
An emerging and underexplored treatment in the
management of tendinopathy is photobiomodulation
(PBM) [14]. While the exact physiological mechanisms
underpinning PBM are yet to be fully described, the pre-
vailing theory is based on the interplay between adeno-
sine triphosphate (ATP), nitric oxide (NO) and
cytochrome c oxidase (complex IV of the mitochondria)
[15]. It is thought that both red and near-infrared (NIR)
light have a high affinity for CCO [15]. During routine
metabolism, or in instances of cellular stress, NO may
competitively bind to CCO, displacing oxygen, slowing
or limiting ATP production. PBM has been suggested to
displace the NO from CCO, allowing oxygen to more
freely interact with CCO, thus enhancing ATP produc-
tion [15]. Despite this mechanism being widely accepted,
there is no evidence to date that shows a direct photo-
biological interaction with CCO [14,16]. Additionally,
there are many other secondary mechanisms by which
PBM may exert its effects. These include an increased
production of reactive oxygen species (ROS), which can
lead to upregulations in gene transcription and down-
stream protein expression [14,17], and additionally may
modulate key immune cells leading to improved tissue
healing and neural fibre inhibition [14,18,19].
At a more fundamental level, how PBM affects tendon
tissue in vitro, and in animal models has been investi-
gated. In vitro PBM appears to influence multiple mech-
anisms related to growth and proliferation. Specifically,
PBM can increase the expression of genes related to pro-
liferating cell nuclear antigen (PCNA) and transforming
growth factor-β1 (TGF-β1) [20,21]; Cyclins E, A, and
B1 [21]; expression of genes related to type I collagen,
decorin [22] and dynamin II [23], all of which are key
regulators of the healing response. Interestingly, PBM
has also been shown to decrease the expression of genes
related to inflammation such as TNF-α[24] and IL-6 in
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 2 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
tenocytes [25]. The positive effects of PBM have also
been observed in animal models of tendinopathy, show-
ing mild improvements in functional healing compared
to non-irradiated controls [26]. However, as with many
areas of study within the field of PBM, a recent review
article reported that the lack of a standardized process
for treating animal tendons with PBM makes compari-
son difficult, and its further development and
standardization should be given priority [27].
The impact of PBM on tendinopathy has been ap-
praised with reviews on specific tendinopathies such as:
lateral elbow tendinopathy [28]; Achilles tendinopathy
[29]; and shoulder tendinopathy [30]; all of which dem-
onstrated mixed effects, possibly due to a lack of consist-
ent PBM application variables between studies. There
has also been a systematic review and meta-analysis of
the effects of PBM on all human tendinopathies, how-
ever it was reported in 2010, and included both random-
ized controlled trials (RCTs) and controlled clinical trials
(CCTs) [31], and again mixed results were reported.
Building on these previous works, and given the pro-
posed universal effects of PBM, the aim of this work was
to synthesize the current evidence describing the impact
of low-intensity red and NIR PBM on pain and function
in all tendinopathy disorders in human patients. Specif-
ically, appraising only RCTs, we analyzed the effects of
PBM on tendinopathy in three domains: Pain, PROMS
and Strength.
Methods
Protocol and registration
This review was prospectively registered in the PROS-
PERO database (registration number:
CRD42020202508). It was also completed and structured
according to the Preferred Reporting Items for System-
atic Reviews and Meta-Analyses (PRISMA) guidelines
[32].
Eligibility criteria
Studies included in this review were any randomized
controlled trials that used up to a class 3B power laser,
or equivalent light sources within the 600 nm –1100 nm
spectrum, to treat any diagnosed tendinopathy or
tendinopathy-related disorders. Given the proposed uni-
versal effects of PBM, and the wide-ranging appraisal
aim of this review, all tendinopathy and tendinopathy-
related disorders were pooled. Comparisons had to be
made to placebo or other clinical interventions in hu-
man adults. Further, the trials needed to report Visual
Analogue Scale (VAS), validated Patient Reported Out-
come Measure (PROM) data and/or changes in muscle
strength. Studies were excluded if they were produced
before the year 2000 given the change in both the diag-
nosis and understanding of tendinopathy [7] and the
changes in PBM application [33] in that time. Articles
unavailable in English were excluded.
Information sources and search strategy
The search terms used in this review were: (Photobio-
modulation OR Low-level laser OR LLLT) AND (ten-
don* OR tendin* OR epicond* OR teno* OR elbow OR
bursitis OR subacromial). The databases that were
searched were: Pubmed, CINAHL, SCOPUS, Cochrane
Database, Web of Science, SPORTSDiscus. This search
was completed by 1st August, 2020. An updated search
was performed in April 2021 and yielded no additional
results. Reference lists of relevant PBM reviews were also
searched. A detailed description of the search can be
found in Table 1 of Additional file 1.
Study selection
The titles and abstract of all the studies yielded in the
initial search were screened by two of the authors (NT
and JF) for eligibility using the Covidence (Melbourne,
Australia) platform. Any disagreements were resolved by
a third author (MH). From here, full-text analysis was
completed by the two of the authors (NT and JF) and
again resolved by a third (MH). The authors of studies
which reported insufficient data for the meta-analysis
were contacted by email, however, were excluded if no
response was given.
Risk of Bias
Two of the authors (NT and JF) assessed the included
studies for bias using the Cochrane Collaboration’s risk-
of-bias tool [34]. Publication bias was assessed by funnel
plot analysis generated by Review Manager Version 4.5
(The Cochrane Collaboration, Denmark), where there
were more than 10 studies to analyze.
Data collection process
Data of interest was extracted individually by two of the
authors (NT and JF), with any disputes or inconsisten-
cies resolved by the addition of a third author (MH), and
then reaching a consensus decision.
Data items
The primary outcomes taken for this study were pain in-
tensity, in the form of the VAS, validated PROMS and
changes in muscle strength. Range of motion measure-
ments were excluded as they are not considered to be a
core domain of tendinopathy [35]. The secondary out-
come taken was reporting of adverse effects.
Summary measures
As the primary measurements were all reported as con-
tinuous data, VAS and PROM data were combined using
the mean difference (MD) statistic, while change in
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 3 of 13
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muscle strength data was analyzed using the standard-
ized mean difference (SMD) statistic (given the hetero-
geneity in measuring muscle strength), using the change
scores between time points. As only three of the in-
cluded studies reported the SD change score [36–38],
the correlation coefficient was calculated to be 0.8 based
on these studies [39]. The data then underwent a sensi-
tivity analysis comparing the meta-analysis results using
a correlation coefficient of 0.2 and 0.8. As no change in
the results were detected with either coefficient, the cor-
relation coefficient of 0.8 was used for the final analysis
VAS data was reported on a scale of 0–10, with data re-
ported on a scale of 0–100 transformed to the 0–10
scale. PROM data was reported on a scale of 0–100.
Studies that reported multiple VAS sub-scales (i.e. VAS
rest, VAS night, etc.) and strength testing measurements
means were averaged, and their standard deviation
pooled according to previously described measures [39].
Studies that reported a 95% confidence interval (CI), and
not the SD, were converted to SD [39].
Synthesis of results
Two authors (NT and JF) completed the analysis using
both Microsoft Excel (Microsoft, USA) and Review Man-
ager Version 4.5 (The Cochrane Collaboration,
Denmark). A random effects meta-analysis was used to
analyze the results, with the I
2
statistic being used to as-
sess study heterogeneity. The trials were grouped ac-
cording to VAS, specific PROM and strength
measurements. Given the variability in design amongst
the included studies, multiple subgroupings were made
according to time points analyzed and comparison treat-
ments and controls. ‘End of treatment’was defined as
end of a 2–4 week course of the treatment intervention,
while ‘Follow Up’was defined as 3 months post-
treatment.
The evidence quality of each outcome was subjectively
assessed using the Grading of Recommendation, Devel-
opment and Evaluation (GRADE) tool [40]. Using the
criteria from Tomazoni, Almeida [41], five factors and
threshold criteria were used to assess the evidence qual-
ity: Risk of Bias: > 25% of trials classified at high risk of
bias; Inconsistency: I
2
> 50%; Indirectness: > 50% of par-
ticipants not related to trial’s target audience; Impreci-
sion: < 400 participants in the comparison for
continuous outcomes; and Publication Bias: funnel plot
if > 10 trials in same comparison [41]. The evidence
quality could be categorized according to four ratings:
High; Moderate; Low; and Very Low. Each time an out-
come did not meet each of the threshold criteria it was
downgraded one level per criteria. For example, if one
measure did not meet the thresholds for risk of bias and
Inconsistency it was classified as low-quality evidence,
downgraded from high-quality evidence.
Results
Search summary
The detailed search strategy is shown in Table 1 of Add-
itional file 1. The initial search strategy yielded 1230 re-
sults, after title and abstract screening of these results,
104 studies remained. When these were subjected to
full-text screening 22 studies were eligible, of which 17
were included in the meta-analysis [36–38,42–55]
(Fig. 1). The five eligible, but excluded studies, were
omitted due to insufficient data, which could not be ob-
tained by contacting the authors [56–60]/ The pooled
studies equated to a total of (n= 835) participants.
Included study characteristics
Participant diagnosis
Of the included studies, one investigated (n= 1) Achilles
Tendinopathy (AT) [53]; one investigated De Quervain’s
Tenosynovitis (DQT) (n=1) [51]; seven (n= 7) investi-
gated Lateral Elbow Tendinopathy (LET) [36,43,45,46,
48,50,52]; one (n= 1) investigated Patella Tendinopathy
(PT) [38]; and seven (n= 7) investigated Sub-acromial
Syndrome/Rotator Cuff Tendinopathy (SAS/RT) [37,42,
44,47,49,54,55] (Table 1).
Interventions
There were a wide array of PBM application variables
used within the included studies. All the studies used
NIR light, ranging from 0.5-5 J/cm
2
, and all studies irra-
diated multiple sites. Additionally, there were a number
of studies that did not report all necessary light applica-
tion variables [36,42,46,47,49,51,54,55] (Tables 1
and 2). Other comparative interventions (“other inter-
ventions”) included: Phonophoresis and Iontophoresis
[43]; ESWT [46]; High-Intensity Laser Therapy (HILT)
[48]; Passive Physiotherapy [37]; and US [51]; with the
remaining studies using exercise alone [36,42,50,52,
53,55], or exercise plus another intervention [45,54].
Only four studies used the WALT guidelines [33] to in-
form their treatment protocols [36,51,53,54] (Tables 1
and 2).
Outcome measures
All the included studies used VAS as an outcome meas-
ure. Of the studies that used PROMS in their measures,
four (k= 4) studies used the Disabilities of the Arm,
Shoulder and Hand (DASH) measure [36,45,50,55];
with one (k= 1) using the Quick DASH (Q-DASH) [48];
two (k= 2) used the Patient Reported Tennis Elbow
Evaluation (PRTEE) [36,43]; two (n= 2) used the Shoul-
der Disability Questionnaire (SDQ) [37,55]; three (k=3)
used the Shoulder Pain and Disability Index (SPADI)
[44,47,49]; and one (k= 1) study used the Victoria In-
stitute of Sport Assessment-Patella Tendon (VISA-P)
[38]. Due to the heterogeneous nature, and limited
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 4 of 13
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numbers of study interventions, only the DASH scores
could be subject to meta-analysis. Additionally, there
were 10 (k= 10) studies that used muscle strength scores
and an outcome measure [36,38,43,45,46,48,50–52,
55] (Table 1). Only five studies reported if any adverse
effects occurred in the trial, of which there were none
[42,44,47,48,55].
Risk of Bias
When pooled together the included studies were judged
to a low risk of bias 68.1% of the time, an unclear risk of
bias 23.5% of the time, and high risk of bias 8.4% of the
time. Largely, the included studies tended to under re-
port the randomization and blinding protocols, with
some studies also failing to report all the required light
parameters, hence being judged as being subject to
‘other bias’(Fig. 2). Publication bias via funnel plot ana-
lysis was not completed as none of the individual forest
plots contained > 10 studies [34].
VAS measures
PBM only versus other interventions only
When compared to other interventions only (Phono-
phoresis, Iontophoresis, ESWT, HILT, CS Injection and
US), PBM only, demonstrated similar effects from
baseline-end of treatment (MD -0.09; 95% CI --0.79 to
0.61; I
2
= 78%; n= 105). The studies in this outcome
were downgraded to very low-quality evidence due to
risk of bias, inconsistency, and imprecision (Fig. 3a).
PBM plus exercise versus sham plus exercise
Overall, PBM plus exercise demonstrated significant re-
ductions in pain levels compared to sham plus exercise
(MD 1.06; 95% CI 0.57 to 1.55; I
2
= 82%; n= 224). The
time period subgroup analysis showed similar results
with, PBM plus exercise creating a more substantial de-
crease in pain at baseline-end of treatment (MD 0.96;
95% CI 0.27 to 1.64; I
2
= 89%; n= 154), and baseline-
follow up (MD 1.22; 95% CI 0.68 to 1.76; I
2
=35%; n=
70). There were no significant between-subgroup differ-
ences found (p= 0.55). The studies in this outcome were
downgraded to low-quality evidence due to inconsist-
ency and Imprecision (Fig. 3b).
PBM plus exercise versus other intervention plus exercise
No significant difference was found between PBM plus
exercise and other interventions (ESWT and US) plus
exercise (MD 0.31; 95% CI −0.07 to 0.70; I
2
= 0%; n=
70). The time period subgroup analysis demonstrated
similar effects on pain within the baseline-end of
Fig. 1 Literature search process according to the PRISMA guidelines
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 5 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
treatment (MD 0.20; 95% CI −0.34 to 0.74; I
2
= 0%; n=
35), and baseline-follow up (MD 0.43; 95% CI −0.12 to
0.97; I
2
= 0%; n= 35) periods. There were no significant
between-subgroup differences found (p= 0.57). The
studies in this outcome were downgraded to moderate-
quality evidence due to imprecision (Fig. 3c).
Proms
DASH: PBM plus exercise versus sham plus exercise
PBM plus exercise demonstrated a significant improve-
ment in the DASH PROM score compared to sham plus
exercise (MD 5.65; 95% CI 0.25 to 11.04; I
2
= 78% n=
112). The time period subgroup analysis showed no sig-
nificant effect of PBM at baseline-end of treatment (MD
2.83; 95% CI −4.56 to 0.70; I
2
= 80%; n= 69), while PBM
plus exercise demonstrated a significant positive effect at
the baseline-follow up period (MD 9.47; 95% CI 5.63 to
13.31; I
2
= 0%; n= 43). There were no significant
between-subgroup differences found (p= 0.12). The
studies in this outcome were downgraded to very low-
quality evidence due to risk of bias, inconsistency and
imprecision (Fig. 4).
Strength measures
PBM only versus other interventions only
When compared to other interventions only (Phono-
phoresis, Iontophoresis, ESWT, HILT, CS Injection and
US), PBM only, demonstrated a significantly decreased
Table 1 Characteristics of included studies
Study First
Author,
Year
Diagnosis Total Participants;
Participants per
group
Intervention Groups Outcomes
Extracted
Treatment
Time
Measurement Time Points
Abrisham
2011 [42]
SAS 80; 40/40 PBM + Exercise, Sham; Laser +
Exercise
VAS Two weeks 1. Baseline; 2. Two weeks
Baktir 2018
[43]
LET 37; 12/13/13 PBM; Phonophoresis;
Iontophoresis
VAS; PRTEE-
t
Three
weeks
1. Baseline; 2. Two Weeks
Bal 2009 [44] SAS 44; 22/22 PBM + Exercise; Exercise Only VAS;
SPADI-t
Two weeks 1. Baseline; 2. Two weeks; 3. Three
month follow up
Celik 2019
[45]
LET 43; 23/22 PBM + Exercise; ESWT + Exercise VAS; DASH Four weeks 1. Baseline; 2. Four weeks; 3. Three
month follow up
Devrimsel
2014 [46]
LET 60; 30/30 PBM; ESWT VAS Four weeks 1. Baseline; 2. Four weeks; 3. Three
month follow up
Dogan 2010
[47]
SAS 52; 30/22 PBM + Exercise; Sham PBM +
Exercise
VAS;
SAPDI-t
Three
weeks
1. Baseline; 2. Three weeks
Emanet 2010
[36]
LET 50; 25/25 PBM + Exercise; Sham PBM +
Exercise
VAS; DASH;
PRETEE-t
Three
weeks
1. Baseline; 2. Three weeks; 3.
Three month follow up
Eslamian
2012 [37]
RT 50; 25/25 PBM + Passive Physiotherapy;
Sham PBM + Passive
Physiotherapy
VAS; SDQ Three
weeks
1. Baseline; 2. Four weeks; 3. Three
month follow up
Kaydok 2020
[48]
LET 59; 30/29 PBM + HILT VAS; QDAS
H
Three
weeks
1. Baseline; 2. Three weeks
Kibar 2017
[49]
SAS 62; 30/32 PBM; Sham PBM VAS;
SAPDI-t
Three
weeks
1. Baseline; 2. Three weeks
Lam 2007
[50]
LET 39; 21/18 PBM + Exercise; Sham + Exercise
Only
VAS; DASH Three
weeks
1. Baseline; 2. Three weeks
Liu 2014 [38] PT 21; 7/7/7 PBM; Exercise Only; PBM +
Exercise
VAS; VISA-P Four Weeks 1. Baseline; 2. Four weeks
Sharma 2015
[51]
DQT 30; 15/15 PBM; US VAS Two Weeks 1. Baseline; 2. Two weeks
Stergioulas
2007 [52]
LET 50; 20/20 PBM + Exercise; Sham + Exercise VAS Four and
Eight
Weeks
1. Baseline; 2. Eight weeks; 3. Two
month follow up
Stergioulas
2008 [53]
AT 40; 20/20 PBM + Exercise; Sham + Exercise VAS Four and
Eight
Weeks
1. Baseline; 2. Four weeks; 3. Eight
Weeks; 4. Three month follow up
Yavuz 2014
[54]
SAS 31; 16/15 PBM + Exercise; US + Exercise VAS;
SPADI-D
Four Weeks 1. Baseline; 2. Four weeks; 3. Three
month follow up
Yeldan, 2009
[55]
SAS 60; 34/26 PBM + Exercise; Sham PBM +
Exercise
VAS; DASH;
SDQ
Three
Weeks
1. Baseline; 2. Three weeks
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
effect from baseline-end of treatment (SMD -0.52; 95%
CI −0.81 to −0.23; I
2
= 0%; n= 105) (Fig. 5a). The stud-
ies in this outcome were downgraded to low-quality evi-
dence due to risk of bias and imprecision.
PBM plus Exercise versus Sham plus Exercise.
Overall, the results demonstrated that PBM plus exer-
cise caused significant increase in strength compared to
sham plus exercise (SMD 0.66; 95% CI 0.11 to 1.21; I
2
=
81%; n= 144). The time period subgroup analysis how-
ever, demonstrated no significant effect for PBM plus
exercise on functional strength measures within both the
baseline-end of treatment (SMD 0.59; 95% CI −0.13 to
−1.31; I
2
= 83%; n= 94) and baseline-follow up period
(SMD 0.82; 95% CI −0.33 to 1.96; I
2
= 87%; n= 50).
There were no significant between-subgroup differences
found (p= 0.74). The studies in this outcome were
downgraded to low-quality evidence due to Inconsist-
ency and Imprecision (Fig. 5b).
GRADE classifications
The quality of evidence classification for each outcome
is located in Table 2 in Additional file 1.
Discussion
The overarching aim of this review was to investigate
the effect of low-intensity red and NIR PBM on pain
and function in patients with tendinopathy and
tendinopathy-related disorders. It was found that when
compared to other interventions, with or without exer-
cise added (Phonophoresis, Iontophoresis, ESWT, HILT,
CS Injection and US), that there is very low-moderate
quality evidence to show that PBM with or without
Table 2 PBM variables of included studies
Study First
Author, Year
PBM light
source;
Wavelength
Light source power output
during treatment (mW)
Fluence per
spot (J/cm
2
)
Treatment
spots
PBM sessions per week;
Total PBM sessions
WALT
recommendations
informed trial?
Abrisham
2011 [42]
‘Laser Device;’
890 nm
Not Reported 2–4 3 5; 10 No
Baktir 2018
[43]
GaAs Laser Diode;
904 nm
0.12 Not Reported 5 5; 15 No
Bal 2009 [44] GaAs Laser Diode;
904 nm
13.2 2 4 5;10 No
Celik 2019
[45]
GaAs Laser Diode;
904 nm
40 2.4 6 3;12 No
Devrimsel
2014 [46]
‘Laser;’850 nm Not Reported Not Reported Not
Reported
2; 10 No
Dogan 2010
[47]
GaAlAs; 850 nm Not Reported 5 5–64–5; 14 No
Emanet 2010
[36]
GaAs Laser; 905
nm
Not Reported 1 2 5; 15 Yes
Eslamian 2012
[37]
Ga-Al-As Laser
Diode; 850 nm
100 4 Up to 10 3; 9 No
Kaydok 2020
[48]
Ga-Al-As Laser
Diode; 904 nm
240 2–4 6 3; 9 No
Kibar 2017
[49]
Ga-Al-As Laser
Diode; 850 nm
Not Reported 4 11 3; 9 No
Lam 2007 [50] Ga-Al-As Laser
Diode; 904 nm
25 2.4 Average 2.4 3; 9 No
Liu 2014 [38] Ga-Al-As Laser
Diode; 810 nm
200 Not Reported 3 6; 24 No
Sharma 2015
[51]
Ga-Al-As Laser
Diode; 830 nm
30–40 3 Not
Reported
3–4; 7 Yes
Stergioulas
2007 [52]
Ga-As; 904 nm 40 2.4 6 1–2; 12 No
Stergioulas
2008 [53]
Ga-Al-As Laser
Diode; 820 nm
30 0.5 6 1–2; 12 Yes
Yavuz 2014
[54]
Ga-Al-As Laser
Diode; 850 nm
Not Reported 3 5
maximum
2–3; 10 Yes
Yeldan, 2009
[55]
GaAs; 904 nm Not Reported Not Reported 5 Maximum Not Reported No
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 7 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
exercise were equally effective at reducing pain. This re-
view also found very low-quality evidence demonstrating
that when PBM is combined with exercise, it results in a
significant improvement in PROMS compared to sham
treatment plus exercise. There was also low-quality evi-
dence demonstrating that other interventions (Phono-
phoresis, Iontophoresis, ESWT, HILT, CS Injection and
US) were significantly better at improving functional
strength measures compared to PBM, while when exer-
cise was added to PBM therapy, it was significantly bet-
ter at restoring functional muscle strength compared to
sham treatment plus exercise.
Despite the small body of somewhat favorable evi-
dence for PBM, as a whole, there were multiple limita-
tions with the studies included in this review. Firstly,
according to the GRADE classification system, all out-
come measure assessed were classified as very low, low,
or moderate quality of evidence. This was largely due to
many of studies been classified as inconsistent (I
2
> 50%)
and imprecise (< 400 participants per outcome measure)
and judged to be at high risk of bias (> 25% trials are
classified as high risk). Although the imprecision could
be addressed with the inclusion of more studies, the fact
that we were not able to assess for publication bias, as
no outcomes had more the 10 included trials, is some-
thing that will have to be addressed in future trials and
reviews. Furthermore, 31.9% of the risk of bias variables
assessed were judged to be of unknown or high-risk of
bias, which should be taken into account when inter-
preting the results of this review.
It is well documented throughout the literature that
the inconsistent nature of PBM experiments, both clin-
ical [41,61] and in vitro [14], are a significant hurdle in
establishing both a concrete physiological mechanism,
and a widely used and accepted set of clinical implemen-
tation guidelines. Appraising the studies included in this
review, we see many differing forms of PBM application,
including total number of treatments, treatment sites,
and irradiation per site. This is understandable given
they are treating different areas of tendon pathology,
however, there were some studies that did not report all
the required treatment variables [36,42,46,47,49,51,
54,55], making exact replication challenging, in the
process affecting the quality of evidence. The WALT
(World Association for Laser Therapy) recommenda-
tions are a set of therapeutic recommendations for clin-
ical and scientific application of red and NIR spectrum
PBM [33]. Only four of the trials in this review refer-
enced the WALT recommendations in their study de-
sign [36,51,53,54], further underlining the need for
higher levels of inter-study consistency.
Heavy strength and plyometric training, in addition to
training load management, appear to be the most effica-
cious exercise modalities to employ during tendinopathy
Fig. 2 Risk of bias summary - review authors’judgements about
each risk of bias item for each included study
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 8 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Fig. 3 VAS: a: Forest plot of comparing PBM only and other interventions (O/Intervention) only; b: Forest plot of the effects of PBM plus exercise
(Exc) versus sham treatment plus exercise; c: Forest plot of the effects of PBM plus exercise versus other interventions plus exercise
Fig. 4 PROMS: Forest plot of comparing PBM plus exercise versus sham + exercise
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 9 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
management [1]. This review demonstrated very low-
quality evidence that PBM could be used as an adjunct
therapy to enhance the effects of exercise rehabilitation.
That said, a limitation of this analysis was that all the ex-
ercise modalities from each study were pooled in each
outcome measure, hence different exercise prescriptions
may have affected the results. Future research in this
area should more stringently control the exercise pre-
scription groups in line with tendinopathy best practice.
Interestingly, this review also found that when compared
to other interventions, PBM was equally as effective at
decreasing pain, however, this was again limited by the
pooling of all other interventions. Many of the other in-
terventions that used a pharmacological anti-
inflammatory agent, such as Phonophoresis, Iontophor-
esis and CS Injection, can cause unwanted patient side
effects [62]. In fact, it is now recommended that practi-
tioners move away from these methods, CS injections in
particular, due to the long-term deleterious tissue effects
they can have [62]. In light of this, PBM may represent a
non-invasive, cost effective and safe alternative to the
more traditional injection and anti-inflammatory based
therapies used in tendinopathy management. However,
more robust trials are needed to elucidate this effect.
To our knowledge only one other systematic review
and meta-analysis has been performed on the effect of
PBM on all tendinopathies previously [31]. This review
demonstrated similar mixed results concerning the ef-
fects of PBM on pain and function in tendinopathy and
similar issues with evidence quality to the present re-
view, despite having fewer studies available for analysis.
Tendinopathy specific systematic review and meta-
analyses have been conducted for shoulder [30] and
Achilles tendinopathy [29] and similarly to this review,
found a mixed efficacy of PBM underpinned by trials of
moderate-very low evidence. Taking these findings to-
gether, it is clear that more widespread and robust RCTs
are needed to better inform the use of PBM in tendino-
pathy management.
The strengths of this review include a detailed search
of multiple databases, as well as additional searches of
paper reference lists. Further, two of the authors per-
formed the entire search process and the risk of bias and
GRADE categorization, with a third author resolving any
disputes. Another limitation of this study was the fact
that all tendinopathies were pooled together as a single
diagnostic entity. Hence, the analysis may not have
accounted for the heterogeneity of tendinopathy disor-
ders. However, the analysis appeared to indicate similar
effects of PBM, regardless of specific diagnosis. More
specific-tendinopathy RCTs are needed to underpin
more robust single-tendinopathy systematic reviews and
Fig. 5 Strength Measures: a: Forest plot of comparing PBM only and other interventions (O/Intervention) only; b: Forest plot of the effects of PBM
plus exercise (Exc) versus sham treatment plus exercise
Tripodi et al. BMC Sports Science, Medicine and Rehabilitation (2021) 13:91 Page 10 of 13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
meta-analyses. Additionally, the exclusion of multiple
studies whose required statistics were unobtainable from
either the paper, or the contact authors may have chan-
ged the study results. As previously stated, the future re-
search focus of PBM for the management of
tendinopathy should be set on performing repeated ro-
bust RCTs that adequately report and justify all treat-
ment parameters and follow the Consolidated Standard
of Reporting Trials (CONSORT) guidelines. This will
firstly better elucidate if PBM is an effective standalone
and/or adjunct therapy for PBM, and secondly if high-
quality evidence is found for this effect, it will underpin
improved treatment guidelines, potentially translating to
improved patient health outcomes.
Conclusion
PBM is an increasingly used treatment modality for a
range of musculoskeletal disorders, however, there are
many questions regarding its mechanisms and true ef-
fectiveness that remain under-investigated and un-
answered. Currently, there is very-low-to-moderate
quality evidence that low-intensity red and NIR PBM is
an effective standalone and exercise-adjunctive treat-
ment for tendinopathy disorders in humans. Further, a
similar quality of evidence demonstrates that it may have
utility as a less-invasive and more risk-averse adjunctive
treatment to more traditional passive interventions.
More robust RCTs that adhere to the CONSORT guide-
lines need to be performed to further elucidate its
effectiveness.
Abbreviations
SAS: Subacromial syndrome; LET: Lateral elbow tendinopathy; RT: Rotator cuff
tendinopathy; PT: Patella tendinopathy; AT: Achilles tendinopathy;
PBM: Photobiomodulation; ESWT: Extracorporeal shock wave therapy;
HILT: High-intensity laser therapy; US: Ultrasound; VAS: Visual analogue scale;
DASH: Disabilities of the arm, shoulder and hand measure; QDASH: Quick
DASH; PRTEE: Patient reported tennis elbow evaluation; SDQ: Shoulder
disability questionnaire; SPADI: Shoulder pain and disability index; VISA-
P: Victoria institute of sport assessment-patella tendon; WALT: World
association for laser therapy; Exc: Exercise; O/Intervention: Other Intervention;
MD: Mean Difference; SMD: Standardized mean difference; CI: Confidence
Interval; mW: Milliwatt; J: Joules; NIR: Near-infrared light; RCTs: Randomized
controlled trials (RCTs); CCTs: Controlled clinical trials; ATP: Adenosine
Triphosphate; NO: Nitric Oxide; CCO: Cytochrome C Oxidase; PROMS: Patient
reported outcome measures; PCNA: Proliferating cell nuclear antigen;
ROS: Reactive oxygen species
Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s13102-021-00306-z.
Additional file 1: Table 1. Review Search Strategy and Results. Table
2. GRADE Classifications.
Acknowledgments
The Authors would like to acknowledge the Australian Government for the
support of NT and JF through RTP training scholarships. JF was also
supported by the the Defence Science Institute and a University of
Melbourne PhD Stipend, and NT by a Victoria University PhD Stipend. All
authors would like to thank the Immunology and Translational Research
Group within the Institute for Health and Sport, Victoria University Australia
for their support.
Authors’contributions
NT was involved in conceptualization, methodology, analysis, writing and
project administration. JF was involved in conceptualization, methodology,
analysis, and writing. MH was involved in conceptualization, methodology,
analysis, and writing. FS was involved in conceptualization, methodology,
and writing. VA was involved in conceptualization, methodology, analysis,
and writing. All authors read and approved the final manuscript.
Funding
This research article was supported by the Defence Science Institute, an
initiative of the State Government of Victoria, Australia.
Availability of data and materials
The Pubmed, CINAHL, SCOPUS, Cochrane Database, Web of Science and
SPORTSDICUS databases were searched for eligible articles in August 2020′.
Additionally, this study was registered with the PROSPERO database
(registration number: CRD42020202508). All data and analysis can be made
available on request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The Authors have no competing interests to declare.
Author details
1
Institute for Health and Sport, Victoria University, Room 1.16, 301 Flinders
Lane, Melbourne, VIC 3000, Australia.
2
First Year College, Victoria University,
Melbourne, Australia.
3
Australian Institute for Musculoskeletal Science (AIMS
S), The University of Melbourne and Western Health, St. Albans, Australia.
4
Department of Medicine-Western Health, Melbourne Medical School, The
University of Melbourne, St. Albans, Australia.
5
Institute for Sustainable
Industries and Liveable Cities, Victoria University, Melbourne, Australia.
Received: 18 February 2021 Accepted: 7 July 2021
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