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Photobiomodulation effects on Achilles tendon pain: a systematic review and meta-

analysis of randomized clinical trials

EMMANUEL S. ROCHA

| ESTHEVAN MACHADO

| FRANCESCA C. SONDA

| KLAUBER D. POMPEO

| PATRÍCIA F.

SANTOS

| MARIANE B. SCHEEREN

| JEAM M. GEREMIA

| MARCO A. VAZ

Biomechanics and Kinesiology Research Group, Exercise Research Laboratory, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Correspondence to:!Marco Aurélio Vaz. Biomechanics and Kinesiology Research Group, Exercise Research Laboratory, Universidade Federal do Rio Grande do Sul,

Porto Alegre, RS, Brazil.

email: marco.vaz@ufrgs.br

https://doi.org/10.20338/bjmb.v16i3.293

HIGHLIGHTS

• Studies with photobiomodulation and Achilles

tendon pain have a high risk of bias.

• The included studies showed very low- to

low-quality evidence.

• There is no photobiomodulation effect in

Achilles tendon pain.

ABBREVIATIONS

CI Confidence intervals

I² inconsistency test

PEDro Physiotherapy Evidence Database

PRISMA Preferred Reporting Items for

Systematic Reviews and

Meta-Analyses

PROSPERO International Prospective

SD Standard deviation

SMD standardized mean difference

PUBLICATION DATA

Received 31 01 2022

Accepted 04 06 2022

Published 01 09 2022

BACKGROUND: Achilles tendon pain is present in tendons’ non-rupture injuries usually exacerbated by

mechanical loading (i.e., overuse injury). Photobiomodulation is a light therapy that may reduce pain in

tendinopathy.

AIM: This systematic review and meta-analysis of randomized clinical trials tested the acute and chronic effects

of photobiomodulation on Achilles tendon pain.

METHOD: Randomized clinical trials were included comparing photobiomodulation with a control group in

patients with Achilles tendon pain. The search included MEDLINE (Pubmed), SCOPUS, EMBASE,

Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials (Cochrane

CENTRAL), LILACS, and Science Direct databases, and manual search until November 2021. The bias’s risk

was assessed by the Cochrane Collaboration bias risk assessment tool and PEDro scale, while the level of

evidence strength by the GRADE. Quantitative analysis through meta-analyzes was performed. The protocol

was registered (PROSPERO-CRD42018091509).

RESULTS: The search yielded 3.239 papers in the seven databases. Five studies were included after

screening, eliminating duplicates, and applying eligibility criteria, and three were included in the meta-analysis.

The meta-analysis (n=79) showed no photobiomodulation acute and chronic effects compared with control

group on Achilles tendon pain (p= 0.45, SMD: 0.28). In the qualitative analysis, three studies showed a high risk,

and two studies a low risk of bias in all characteristics. GRADE analysis showed very low- to low-quality

evidence of the studies.

CONCLUSION: There is no photobiomodulation effect in Achilles tendon pain. Due to the very low and low

strength of evidence, new studies with better methodological quality should be conducted to improve the level of

evidence.

INTRODUCTION

Achilles tendon disorders are related to overuse injuries and complete,

spontaneous rupture

. However, the number and incidence of Achilles tendinopathy cases

increased in the last decade

2,3

. Tendinopathy is a term used to indicate a non-rupture

injury in the Achilles tendon that is exacerbated by mechanical loading. The Achilles

tendon is often exposed to different stresses (e.g., tension, compression, and shear), and

when these loads exceed the tendon’s physiological capacity, the Achilles tendon is

exposed to a cumulative cycle of injury with inflammation and repair. These cycles lead to

swelling and pain, which characterizes tendinopathy

A common symptom in patients with tendinopathy is pain

, which changes their

movement pattern. This pain and swelling in the posterior aspect of the ankle make daily-

life activities difficult to be executed. The pain increases after high tendon loading

conditions such as running hills, stairs, or running on toes

. Tendinopathy is characterized

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by collagen disruption/tearing, inflammation, and tenocyte response

4,6,7,8

. An inflammatory

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response in the tendon is seen when a tendon (and its blood supply) is ruptured or

lacerated, with a large immune cell and tenocyte response increases protein production

and tendon size. The tenocyte is primarily responsible for maintaining the extracellular

matrix in response to its environment. Thus, changes in tendon load and biochemical

changes will be sensed by the tendon cells and result in a cascade of responses (cell

activation, proteoglycan expression and changes in collagen type)

An interesting strategy for treating Achilles tendinopathy is photobiomodulation

Photobiomodulation interventions involve the energy coming from monochromatic light

sources that are used in a large scale with therapeutic objectives

. The use of

photobiomodulation therapy has been growing over the years, being a low-cost therapy

with low adverse effects. Preview studies investigated the phototherapy effectivity in the

Achilles tendon healing in rats and observed an increase of type I collagen synthesis

11,12

The energy absorbed by the mitochondria during light therapy stimulates ATP production

and increases intracellular calcium concentration resulting in tenocytes proliferation and

collagen synthesis

The photobiomodulation effect on the tendinopathy process (in female aged rats

with reduced type I collagen)

restored type I collagen levels. The phototherapy per point

application also reduced inflammation and pain in activated Achilles tendinopathy

Previous studies investigated the photobiomodulation’s effectivity in the Achilles tendon

healing in rats and observed increased type I collagen synthesis

12,15

. More recently, the

use of photobiomodulation therapy for anti-inflammatory action, with local and systemic

effects, is being studied. In Achilles tendinopathy, a reduction in the inflammatory process

was observed after photobiomodulation

. Photobiomodulation was shown to acutely

reduce inflammation and pain in Achilles tendinopathy patients

. However, another study

using the World Association for Laser Therapy’s parameters did not find clinical

effectiveness in adding photobiomodulation to eccentric exercises for the treatment of

Achilles tendinopathy

, showing no photobiomodulation’s aditional benefical effect.

Two recent systematic reviews verified the photobiomodulation effect on pain in

patients with tendinopathies

19,20

. Doyle et al.

found five relevant studies indicating that

photobiomodulation decreases pain from baseline measurements. However, from their five

included studies, only two studies

21,22

indicated clinical effectiveness in pain when

comparing photobiomodulation with placebo treatment. Therefore, the inconsistent findings

on the photobiomodulation clinical effects to decrease tendinopathy pain may not be

warranted

. Nevertheless, this systematic review did not perform a meta-analysis and

quality of evidence evaluation. In addition, they included studies with tendinopathies at

different regions of the body. Martimbianco et al.

showed that only two studies from four

trials demonstrated positive effects of photobiomodulation on Achilles tendinopathy

17,22

However, they did not show the studies’ quality of evidence analysis.

Based on these studies’ results, a new systematic review that includes only

randomized clinical trials on tendinopathy pain reduction due to photobiomodulation

therapy is necessary. In this direction, we wanted to know if photobiomodulation is more

effective to reduce pain than placebo or other interventions (e.g., aloe gel) in Achilles

tendinopathy patients. This systematic review with meta-analysis followed the GRADE

recommendations of randomized clinical trials while investigating the photobiomodulation

effect on Achilles tendon pain.

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METHODS

The systematic review and meta-analysis were conducted and reported according

to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)

guidelines

. The study was registered at the International Prospective Register of

Systematic Reviews (PROSPERO) with the registration number CRD42018091509. The

study selection, data extraction, methodological quality of the included studies, and the

certainty of evidence were conducted by two independent investigators (EM and FCS).

When there was disagreement between the reviewers’ results, a third reviewer (ESR) was

consulted to reach a consensus.

Data sources and search strategy

The studies were selected from the electronic databases MEDLINE (using Pubmed),

SCOPUS, EMBASE, Physiotherapy Evidence Database (PEDro), Cochrane Central

search was performed until November 2021. In addition, a manual search was done in the

references of published studies on the subject. Controlled and uncontrolled descriptors

were used for population, assessment, and outcome (Table 1).

Table 1. Search strategy using MESH terms on the PUBMED.

Terms for search

MESH terms used

Participants

"Achilles Tendon"[Mesh] OR "Achilles Tendon" OR “Tendon, Achilles” OR “Calcaneal Tendon” OR “Calcaneal

Tendons” OR “Tendon, Calcaneal” OR “Tendons, Calcaneal” OR “Tendo Calcaneus” OR "Tendon Injuries"[Mesh] OR

"Tendon Injuries" OR “Injuries, Tendon” OR “Injury, Tendon” OR “Tendon Injury” OR "Tendinopathy"[Mesh] OR

“Tendinopathies” OR “Tendonopathy” OR “Tendonopathies” OR “Tendinosis” OR “Tendinoses” OR “Tendonosis” OR

“Tendonoses” OR “Tendinitis” OR “Tendinitides” OR “Tendonitis” OR “Tendonitides” OR "Tendons"[Mesh] OR

“Tendon” OR “Tendons, Para-Articular” OR “Para-Articular Tendon” OR “Para-Articular Tendons” OR “Tendon, Para-

Articular” OR “Tendons, Para Articular” OR “Tendons, Paraarticular” OR “Paraarticular Tendon” OR “Paraarticular

Tendons” OR “Tendon, Paraarticular” OR “Epotenon” OR “Epotenons” OR “Endotenon” OR “Endotenons” OR

"Rupture, Spontaneous"[Mesh] OR "Rupture, Spontaneous” OR “Ruptures, Spontaneous” OR “Spontaneous

Rupture” OR “Spontaneous Ruptures” OR "Rupture"[Mesh] OR "Rupture” OR "Ruptures" OR “Achilles tendon rupture”

Intervention

"Phototherapy"[Mesh] OR "Phototherapy" OR “Phototherapies” OR “Therapy, Photoradiation” OR “Photoradiation

Therapies” OR “Therapies, Photoradiation” OR “Light Therapy” OR “Light Therapies” OR “Therapies, Light” OR

“Therapy, Light” OR “Photoradiation Therapy” OR "Low-Level Light Therapy"[Mesh] OR “Light Therapies, Low-Level”

OR “Light Therapy, Low-Level” OR “Low Level Light Therapy” OR “Low-Level Light Therapies” OR “Therapies, Low-

Level Light” OR “Therapy, Low-Level Light” OR “Photobiomodulation Therapy” OR “Photobiomodulation Therapies” OR

“Therapies, Photobiomodulation” OR “Therapy, Photobiomodulation” OR “LLLT” OR “Laser Therapy, Low-Level” OR

“Laser Therapies, Low-Level” OR “Laser Therapy, Low Level” OR “Low-Level Laser Therapies” OR “Laser Irradiation,

Low-Power” OR “Irradiation, Low-Power Laser” OR “Laser Irradiation, Low Power” OR “Low-Power Laser Therapy” OR

“Low Power Laser Therapy” OR “Laser Therapy, Low-Power” OR “Laser Therapies, Low-Power” OR “Laser Therapy,

Low Power” OR “Low-Power Laser Therapies” OR “Low-Level Laser Therapy” OR “Low Level Laser Therapy” OR “Low-

Power Laser Irradiation” OR “Low Power Laser Irradiation” OR “Laser Biostimulation” OR “Biostimulation, Laser” OR

“Laser Phototherapy” OR “Phototherapy, Laser”

Study design (Robinson

and Dickersin 2002)

((randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random

allocation[mh] OR double-blind method[mh] OR single-blind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR

("clinical trial"[tw]) OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND (mask*[tw] OR blind*[tw])) OR ("latin

square"[tw]) OR placebos[mh] OR placebo*[tw] OR random*[tw] OR research design[mh:noexp] OR follow-up

studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control*[tw] OR prospectiv*[tw] OR

volunteer*[tw]) NOT (animal[mh] NOT human[mh]))

Eligibility criteria

A PICOT approach was applied to formulate the research question. This

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systematic review included randomized clinical trials that compared photobiomodulation

versus control group in individuals with Achilles tendon disorders (e.g. acute or chronic

tendinopathy) that included pain as a symptom until November 2021. In order to avoid a

risk of bias for language, no restriction of language and no restriction of publication year

was imposed. Systematic review studies, letters to the editor, and editorials were

excluded. The inclusion criteria were: i) being a randomized controlled trial; ii) be

conducted with an individual with Achilles tendon disorders; and iii) use

photobiomodulation therapy by the low-level laser therapy.

Study selection

In the first phase of the selection, the reviewers assessed the titles and abstracts

of the studies identified by the search strategy. All the abstracts that did not give sufficient

information regarding the inclusion and exclusion criteria were selected to assess the

complete article. In the second stage, the reviewers assessed the complete articles and

selected the studies following the eligibility criteria. Homogeneous studies (patient

characteristics, number of participants, age, and similar details of the intervention) were

included in the meta-analysis.

Data extraction

A standardized worksheet was used to extract the data in the meta-analysis. Data

extracted were the average value of the outcomes, the standard deviation, and the number

of subjects for all outcomes. Specifically, the average pre- and post-intervention values

were extracted, as well as the pre- and post-intervention standard deviation (SD) and the

number of participants. These data were extracted for both the control group and the

photobiomodulation group. We used the delta values - the difference between the final

value (post) and the initial value (pre) - of the outcome for each group in the meta-analysis.

In addition, data were extracted to characterize the included studies. This data

included the authors and year of publication, sex, and age of the participants, number of

participants, characteristics of the intervention performed (total duration, weekly sessions,

time of each session and total irradiated energy), as well as statistical results related to the

outcome investigated and the authors’ conclusion.

Data items (outcome)

Our primary outcome was pain. Other outcomes [resumption of training; return to

play; functional ability; tendon thickness; tendon vascularization; PGE2 (prostaglandin E2)

concentrations; morning stiffness severity; crepitation; tenderness; active ankle

dorsiflexion; functionality; and tendon thickness] were exported and are presented in the

results section.

Quality appraisal and risk of bias

The risk of bias was evaluated according to the PRISMA recommendation

Study quality assessment included adequate sequence generation, allocation

concealment, blinding of participants and personnel, blinding of outcome evaluators, use of

intention-to-treat analysis, and description of losses and exclusions and was assessed by

the Cochrane Collaboration bias risk assessment tool

The PEDro scale evaluated the quality assessment of the included studies. PEDro

scores of 6 points or higher were classified as “high quality”, whereas studies with 5 points

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or lower were classified as “low quality”

25,26

. PEDro scores were not used as

inclusion/exclusion criteria but rather as a basis for best-evidence synthesis and to discuss

the studies’ strengths and weaknesses.

Synthesis of results

Initially, the authors and year of the studies, the mean, standard deviation, and the

number of subjects were extracted. As the outcome presented the same unit of measure

but was analyzed by different scales, standardized mean difference (SMD) between the

means was used. The delta values (mean post-value minus the pre-value, if the groups

were different at baseline) or the final values (used if the groups were equal at baseline)

were used depending on the included studies’ results. SMDs were categorized as small

(0.59), medium (0.6 - 1.19) or large (1.20)

. Posteriorly, the meta-analysis was calculated

using a random-effect model and effect measures for continuous outcomes. Confidence

intervals (95% CI) were determined, and p≤0.05 was adopted as the significance level.

The statistical heterogeneity of the effects was assessed using the inconsistency test (I²),

in which values above 25% and 50% were considered as indicative of moderate to high

heterogeneity, respectively

. If there was moderate or high heterogeneity between the

studies, sensitivity and subgroup analyzes (e.g., duration of intervention) was performed.

All analyzes were performed using the program Review Manager, Version 5.3 (Cochrane

Collaboration).

Summary of evidence

The quality of evidence was assessed using the GRADE approach

. The quality

of evidence of the included studies refers to a body of studies and not to individual studies.

Some factors, such as the risk of bias, inconsistency, indirectness, imprecision, and

publication bias, are associated with this judgment, and they may lead to upgrading or

downgrading the quality of evidence of an outcome from a group of studies. The quality of

evidence can be presented in four categories: high (enough evidence in the estimate of the

effect), moderate (the true effect is close to the estimate of the effect), low (the confidence

of the effect is limited), and very low (little confidence of the effect estimate)

RESULTS

Study selection

The search by the defined terms yielded 3.239 studies. After screening all study

titles and eliminating duplicates from the different databases, 64 potentially eligible studies

were identified. Following the abstract examination, 39 studies remained included.

However, the full-text assessment showed that only five studies confirmed all criteria and,

thus, more than twenty-four studies were excluded from further analysis. The screening of

the reference lists of the included studies did not provide additional eligible studies. From

these five included studies, four were included in the meta-analysis (one was excluded

because it used a pharmacological cream with the intervention; Figure 1). All five studies

were evaluated qualitatively.

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Figure 1. Flow diagram based on Moher, Liberati et al. (2009).

Study characteristics

The characteristics of the five included studies are described in Table 2 and Table

3. Table 2 shows a large variability in the intervention duration from 1 session (one day) to

12 sessions (up to eight weeks) and photobiomodulation power density (20 to 1670

mW/cm

); however, it also presents a small variability in the light therapy wavelength (810

to 980 nm). Table 3 shows a large variability of the participants’ number (7 to 80). In

addition, one study applied another intervention (i.e., aloe gel) than placebo as control

group

, and three studies combined the photobiomodulation application with eccentric

exercise during the intervention period

18,22,32

Records identified through

database searching

Pubmed (n= 111)

SCOPUS (n= 2.729)

EMBASE (n= 72)

PEDro (n= 50)

Cochrane (n= 24)

LILACS (n= 43)

Science Direct (n= 210)

Total (n =3.239)

Screening

Included

Eligibility

Identification

Additional records identified

through other sources

(n =0)

Records after duplicates removed

(n= 3.163)

Records screened

(n= 3.163)

Records excluded

(n= 3.124)

Full-text articles

assessed for eligibility

(n = 39)

Full-text articles excluded,

with reasons:

No AT patients (n =7)

Clinical cases for AT (n= 2)

Review (n=1)

No intervention with

phototherapy (n= 10)

Missing data (n=1)

Conference paper (n=1)

Editorial (n=1)

Experimental study (n=1)

Studies included in

qualitative synthesis

(n= 5)

Studies included in

quantitative synthesis

(meta-analysis)

(n= 4)

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Table 2.!Photobiomodulation parameters.

Parameters

Ammendolia et al.,

(2016)

Bjordal et al.,

(2006)

Stergioulas et al.,

(2008)

Tumilty et al.,

(2012)

Tumilty et al.,

(2016)

Duration of

intervention

10 sessions (daily session)

1 session

12 sessions

(2x/week - first 4 weeks;

1x/week - second 4 weeks)

12 sessions

(3x/week for 4 weeks)

8 sessions

(2x/week for 4

weeks)

Wavelength

904 nm

820 nm

810 nm

810 and 980 nm

Optical output

Did not present

30 mW

100 mW

5.000 mW

Irradiation area/

spot size

Did not present

0.5 cm²

0.07 cm²

3 cm²

Power density

25 mW/cm² (pulsed mode)

20 mW/cm².

60 mW/cm²

100 mW/cm²

1.670 mW/cm²

Number of

irradiation points

Did not present

Sweeping

motion from the

calcaneus to 10 cm

proximal

Energy per point

in each session

Did not present

1.8 J

0.9 J

3 J

150 J

Total energy per

session

Did not present

5.4 J

18 J

450 J

Total energy

delivered

in treatment

Did not present

5.4 J

64.8 J

216 J

3.600 J

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Table 3. Characteristics of the included studies. Y means year; LLLT: low-level laser therapy; VAS: Visual analog scale.

STUDY

DISORDER

SAMPLE

OUTCOMES

MEASUREMENT

CONTROL (CG)

RESULTS

CONCLUSION

QUALITY

ASSESSMENT

(PEDRO SCORE)

mmendolia et al

(2016)

Tendinopathy (n=35)

35 elite

volleyball

athletes

(1) Pain

intensity;

(2) Resumption

of training;

(3) Return to

play.

(1) Visual

analogue

scale;

(2) and (3)

days.

3 ml gel (aloe

barbadensis

extract)

3x/day by 10

days

(1) Pain relief in 10 days in CG;

(2) LLLT group return training

earlier than CG;

(3) CG return to play earlier than

LLLT

Healing tendinopathy in a

short time, using a topical

therapy based on

micronutrient as a gel, that

the athletes can self-

administer several times a

day.

Low Quality

(4/10)

jordal et al

(2006)

Pain (n=7)

Patients

recruited

through primary

care by doctors

and

physiotherapists

(1) Pain

intensity;

(2) Functional

ability;

(3) Tendon

thickness;

(4) Tendon

vascularization;

(5) PGE

concentrations.

(1) Pressure

pain threshold

in painful spot

(2) distance in

the single leg

hop test;

(3) Caliper;

(4) Doppler;

(5)

Microdialysis.

Placebo.

(1) Non-significant decrease in the

pain after the treatment;

(2) Both groups showed a

decrease in the single jump hop

test after treatment;

(3) They did not show the result.

(4) No significant differences

between groups were observed

after treatment;

(5) In LLLT group a small decrease

in PGE

concentration was seen

first one hour after treatment, and

then gradually decreasing from

baseline at the last time point 105

minutes after treatment. CG, PGE

concentrations increased gradually

in the period after treatment from

baseline to at the last observation.

LLLT can be used to

reduce inflammatory

musculoskeletal pain.

High Quality

(7/10)

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tergioulas et al

(2008)

Tendinopathy (n=20)

Patients self-

referred or

referred by their

physician for

treatment of

their Achilles

tendinopathy.

(1) Pain during

activity;

(2) Morning

stiffness

severity;

(3) Crepitation;

(4) Tenderness

(5) Active ankle

dorsiflexion.

(1) 100 mm

VAS;

(2) 100 mm

VAS;

(3) 100 mm

VAS;

(4) 40 mm

VAS;

(5) Goniometry.

Placebo.

(1) Pain was significantly lower in

the LLLT group than in CG;

(2), (3), (4) and (5) were

significantly better (P < .05) in the

LLLT group than in the CG.

LLLT seems to be a safe

and effective method for

more rapid recovery when

combined with an eccentric

exercise regimen.

High Quality

(7/10)

umilty et al

(2012)

Tendinopathy (n=40)

Diagnosis of

Achilles

tendinopathy

affecting the

midportion of

the tendon.

(1)

Functionality;

(2) Pain.

(1) VISA-A

questionnaire

(2) Numeric

Pain Rating

Scale (score

between 0 and

10)

Placebo

(1) favored to the CG;

(2) LLLT group displayed inferior

numeric pain scores initially but

failed to demonstrate any superior

gains that may have resulted from

the adjunct laser treatment at all

other assessment points.

Clinical effectiveness of

adding LLLT to eccentric

exercises for the treatment

of Achilles’ tendinopathy

has not been

demonstrated.

High Quality

(10/10)

umilty

t al

(2016)

Tendinopathy (n=80)

Patients with a

diagnosis of

Achilles

tendinopathy

greater than 3

months.

(1)

Functionality;

(2) Pain;

(3) Tendon

thickness.

(1) VISA-A

questionnaire

(2) Numeric

Pain Rating

Scale (score

between 0 and

10)

(3) Ultrasound

Placebo.

(1) all groups had improved their

VISA-A

(2) Pain decreased for all groups.

(3) Tendon thickness reduced

significantly over the course of the

intervention, but there was no

significant difference in these

changes between groups at 12

weeks.

Photobiomodulation using

the parameters stated

above as adjunct to

eccentric exercise can

induce added benefit at 12

weeks

High Quality

(9/10)

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Analysis of the risk of bias and methodological quality

The bias risk analysis results are presented in Figure 2. The analysis was made

considering the five included studies. In Figure 2, we have six data points because the

Tumilty et al.

was duplicated due to the two different groups’ comparisons of

photobiomodulation versus placebo. Bjordal et al.

, Ammendolia et al.

, and Stergioulas

et al.

had an unclear risk of bias for their reporting not being registered on clinical trials.

Bjordal et al.

and Ammendolia et al.

had a high risk of bias for incomplete outcome

data because they did not show an intend-to-treat analysis. Tumilty et al.

and Tumilty et

al.

had a low risk of bias for all analyzed biases, and therefore they were considered the

best methodological studies.

Figure 2. Risk of bias of the included studies.

PEDro scale analyses of the included studies are presented in Table 4.

Ammendolia et al.

was the only study with low quality (4/10), whereas the other included

studies were classified as high quality by the PEDro scale score

25,26

, with the highest

score being obtained by Tumilty et al. 18 with 10/10 points. Only criteria 1, 2, and 10 of the

PEDro scale were contemplated in all studies. However, the GRADE approach presented

a very low quality for the four studies with pain as the outcome, including those that

analyzed pain up to 8 weeks (Table 5). In addition, three studies that analyzed pain up to 4

weeks presented a low quality due to the risk of bias, inconsistent results, and imprecision

(Table 5).

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Table 4. PEDro scale score of the included studies. N: No; Y: Yes.

Studies

Questions

Ammendolia

et al., (2016)

Bjordal

et al., (2006)

Stergioulas

et al., (2008)

Tumilty

et al., (2012)

Tumilty

et al., (2016)

1. Eligibility criteria were specified

2. Subjects were randomly allocated to groups

3. Allocation was concealed

4. The groups were similar at baseline

5. There was blinding of all subjects

6. There was blinding of all therapists who administered the therapy

7. There was blinding of all assessors who measured at least one

key outcome

8. Measures of at least one key outcome were obtained from more

than 85% of the subjects initially allocated to groups

9. All subjects for whom outcome measures were available received

the treatment or control condition as allocated or, where this was not

the case, data for at least one key outcome was analyzed by

“intention to treat”

10. The results of between-group statistical comparisons are

reported for at least one key outcome

11. The study provides both point measures and measures of

variability for at least one key outcome

Total

4/10

7/10

10/10

9/10

Table 5. Quality of evidence using the GRADE approach.

Certainty assessment

Absolute

Certainty

Outcome

Type

ROB

Inconsistency

Indirectness

Imprecision

PBMT

Placebo

(95% CI)

Pain

RCT

serious

very serious

not serious

very serious

124

0.08

[-0.28, 0.44]

VERY

LOW

Pain

(up to 4 weeks)

RCT

not serious

very serious

0.23

[-0.20, 0.66]

LOW

Pain

(up to 8 weeks)

RCT

serious

very serious

not serious

very serious

-0.03

[-0.60, 0.54]

VERY

LOW

RCT: Randomized clinical trial; ROB: Risk of Bias; a: one study with limitation in design; b: moderate heterogeneity; c: large confidence interval; PBMT:

photobiomodulation.

The meta-analysis with 79 patients with Achilles tendon pain showed no

photobiomodulation effect compared with the control group (p= 0.45, SMD: 0.28, CI: -0.45

– 1.01). However, as the heterogeneity was very high (I²=78%), we conducted a subgroup

analysis for the intervention duration and a sensitivity analysis without a study that had a

high risk of bias (Figure 2), and therefore the heterogeneity decreased (I²=19%). Even with

the sensitivity analyzes, the result remained the same, with no photobiomodulation effect

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for Achilles tendon pain (p=0.30, SMD: 0.23, CI: -0.2 – 0.66).

DISCUSSION

This systematic review with meta-analysis summarizes the existent evidence on

the photobiomodulation effects on Achilles tendon pain. The aim was to answer if

photobiomodulation therapy is more effective in reducing Achilles tendon pain compared

with a control group. Our main results showed no photobiomodulation effect in patients

with Achilles tendon pain. In addition, we found a large variability in the intervention

durations and photobiomodulation parameters, making between-interventions comparisons

difficult.

A recent review of the photobiomodulation effect on tendinopathies

showed a

beneficial effect for the tendinopathies’ treatment. However, although they showed a

significant decrease in pain from baseline, its use is no better than placebo or traditional

treatments such as ultrasound, moist heat packs, electrical stimulation, or therapeutic

exercise to reduce pain associated with tendinopathy

It is important to highlight that tendon pain is related to function, and tendinopathy

decreases the ability of the muscle to repeatedly generate appropriate force that enables

the tendon to store and release energy for movement. However, these changes in muscle-

tendon function also occur in the presence of structural pathology, independent of pain

One study

showed that pain decreased in the photobiomodulation group compared with

the placebo group for all evaluation moments (fourth, eighth, and twentieth week).

However, these authors used photobiomodulation combined with eccentric exercise, which

also present clinical benefits to patients with tendinopathy due to the high mechanical load

that stimulates matrix remodeling (degradation and synthesis)

, modulating tendon

structure and improving function

A recent systematic review

showed that three of the included studies combined

photobiomodulation with eccentric exercise, and just one of them demonstrated pain relief.

Therefore, the eccentric exercise effect seems to be more important for the resolution of

tendinopathy than photobiomodulation alone. In addition, they assessed the same level of

evidence by GRADE found by us, which was classified as very low to low, suggesting that

better quality studies are needed to clarify this point.

We observed that the included studies had some methodological limitations (table

4 and figure 2), and only one study had an excellent methodological procedure and low

risk of bias

. This study aimed to determine the most clinically effective loading regimen

for Achilles tendinopathy and determine if any extra benefit could be gained from adding

photobiomodulation combined with eccentric exercises. The authors found that the pain

decreased for all patients after the exercise intervention. Adding photobiomodulation to the

treatment provided additional gains, but only to the group receiving the combination of

photobiomodulation with two eccentric exercise sessions per week. Thus, it seems that the

combined effect of exercise, especially eccentric exercises, with the photobiomodulation

therapy is more important than this light therapy alone. However, Martin et al.

reached

the conclusion of not recommending the use of photobiomodulation intervention on

Achilles tendinopathy.

One study included in our review suggested that the use of photobiomodulation

and the use of a gel-based on aloe barbadensis extract in volleyball athletes with

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tendinopathy should reduce the pain

. They showed that the control group (aloe gel) had

pain relief in 10 days and returned to play earlier than the photobiomodulation group.

However, this study was considered with a high risk of bias and the worst score on the

PEDro scale (4/10). For the authors, it is because the gel used contained micronutrients,

including: extract of Arnica montana (anti-inflammatory), extract of Harpagophytum

procumbens (inhibition of induction of the expression of a gene pro-inflammatory) and

tocopherol (anti-inflammatory).

Information about photobiomodulation parameters used for the interventions were

not standardized and/or were poorly described, with incomplete information, making the

analysis and comparison of the results between studies difficult. The information of these

parameters is very important for the clinical decision making of clinicians

. For example,

the recommendation for the photobiomodulation treatment irradiation frequency is targeted

at ~65 or ~170 J/cm

by the end of the treatment

. Photobiomodulation would reduce pain

in tendinopathy if a proper treatment procedure (including exposure at the skin directly

overlaying the injured tendon daily or every second day for at least 2 to 4 weeks) and the

location-specific dose is used (power density and dose within a suggested optimal range)

Strength and limitations

We used a systematic approach with two independent reviewers processing the

articles for eligibility. In addition, a comprehensive search of several databases following

the recommendations proposed by the Cochrane Back Review Group, and no language

limitations were set to avoid missing relevant articles. Furthermore, the risk of bias of the

included studies was assessed using PEDRO and Cochrane scale, meta-analysis, and the

quality of evidence was assessed using the GRADE recommendations. Furthermore, we

registered the review protocol before starting the research, ensuring the transparency of

the review process as suggested by the PRISMA statement.

A limitation of this review is the low number of articles identified on the topic that

met the eligibility criteria stipulated for the present study and the limited number of articles

selected. Moreover, the studies used very heterogeneous protocols and instruments for

the analyses of the outcomes. For example, the discrepancy in sample sizes between the

studies; heterogeneity of the population; different parameters of photobiomodulation used;

the low and moderate items at risk of bias of the studies were some of the limitations

found.

Further attention should be taken in reporting photobiomodulation therapy

parameters and used devices. These parameters should be shown in detail, in order to

provide accurate information for the reader and allowing the study replication by other

scientists

Finally, more research is needed in this area with greater sample size, better

methodological design, and detailed photobiomodulation therapy parameters to increase

the quality of evidence and allow a better conclusion regarding the photobiomodulation

effects on pain in patients with Achilles tendinopathy.

CONCLUSION

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There is no effect of the photobiomodulation application alone only in Achilles

tendon pain in patients with Achilles tendinopathy. Few randomized clinical trials analyzed

the photobiomodulation effects on Achilles tendon pain. Photobiomodulation seems do not

to provide additional gains to the eccentric exercise program.

Despite the detailed analysis of the individual studies, results must be viewed with

caution due to the very low- to low-quality evidence of the reviewed studies. Therefore,

additional high-quality studies are needed to shed light on the photobiomodulation effects

in Achilles tendon pain, thereby providing evidence-based scientific support for health

professionals' clinical practice.

REFERENCES

1. Jarvinen TA, Kannus P, Maffulli N, Khan KM. Achilles tendon disorders: etiology and

epidemiology. Foot Ankle Clin. 2005;10:255-266. doi: 10.1016/j.fcl.2005.01.013.

2. De Jonge S, Van Den Berg C, De Vos RJ, Van Der Heide HJ, Weir A, Verhaar JA, et al.

Incidence of midportion Achilles tendinopathy in the general population. Br J Sports Med.

2011;45:1026-1028. doi: 10.1136/bjsports-2011-090342.

3. Lagas IF, Fokkema T, Verhaar JaN, Bierma-Zeinstra SMA, Van Middelkoop M, De Vos RJ.

Incidence of Achilles tendinopathy and associated risk factors in recreational runners: A

large prospective cohort study. J Sci Med Sport. 2020;23:448-452.

doi: 10.1016/j.jsams.2019.12.013.

4. Scott A, Backman LJ, Speed C. Tendinopathy: Update on Pathophysiology. J Orthop

Sports Phys Ther. 2015;45:833-841. doi: 10.2519/jospt.2015.5884.

5. Chinn L, Hertel J. Rehabilitation of ankle and foot injuries in athletes. Clin Sports Med.

2010;29:157-167, table of contents. doi: 10.1016/j.csm.2009.09.006.

6. Cook JL, Rio E, Purdam CR, Docking SI. Revisiting the continuum model of tendon

pathology: what is its merit in clinical practice and research? Br J Sports Med.

2016;50:1187-1191. doi: 10.1136/bjsports-2015-095422.

7. Longo UG, Ronga M, Maffulli N. Achilles Tendinopathy. Sports Med Arthrosc Rev.

2018;26:16-30. doi: 10.1097/JSA.0000000000000185.

8. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint

Surg Am. 2005;87:187-202. doi: 10.2106/JBJS.D.01850.

9. Takenori A, Ikuhiro M, Shogo U, Hiroe K, Junji S, Yasutaka T, et al. Immediate pain relief

effect of low level laser therapy for sports injuries: Randomized, double-blind placebo

clinical trial. J Sci Med Sport. 2016;19:980-983. doi: 10.1016/j.jsams.2016.03.006.

10. Enwemeka CS. Low level laser therapy is not low. Photomed Laser Surg. 2005;23:529-

530. doi: 10.1089/pho.2005.23.529.

11. Wood VT, Pinfildi CE, Neves MaI, Parizoto NA, Hochman B, Ferreira LM. Collagen

changes and realignment induced by low-level laser therapy and low-intensity ultrasound

in the calcaneal tendon. Lasers Surg Med. 2010;42:559-565. doi: 10.1002/lsm.20932.

BJMB! ! ! ! ! !!!!!!!!Systematic Review and Meta-Analysis

Brazilian(Journal(of(Motor(Behavior(

(

Rocha et al.

2022

VOL.16

N.3

https://doi.org/10.20338/bjmb.v16i3.293

236 of 239

236 of 235

12. Chen MH, Huang YC, Sun JS, Chao YH, Chen MH. Second messengers mediating the

proliferation and collagen synthesis of tenocytes induced by low-level laser irradiation.

Lasers Med Sci. 2015;30:263-272. doi: 10.1007/s10103-014-1658-5.

13. Marques ACF, Albertini R, Serra AJ, Da Silva EaP, De Oliveira VLC, Silva LM, et al.

Photobiomodulation therapy on collagen type I and III, vascular endothelial growth factor,

and metalloproteinase in experimentally induced tendinopathy in aged rats. Lasers Med

Sci. 2016;31:1915-1923. doi: 10.1007/s10103-016-2070-0.

14. Bjordal JM, Lopes-Martins RaB, Iversen VV. A randomised, placebo controlled trial of low

level laser therapy for activated Achilles tendinitis with microdialysis measurement of

peritendinous prostaglandin E2 concentrations [with consumer summary]. Br J Sports

Med. 2006 Jan;40(1):76-80. 2006.

15. Wood VT, Pinfildi CE, Neves MA, Parizoto NA, Hochman B, Ferreira LM. Collagen

changes and realignment induced by low-level laser therapy and low-intensity ultrasound

in the calcaneal tendon. Lasers Surg Med. 2010;42:559-565. doi: 10.1002/lsm.20932.

16. Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of

photobiomodulation. AIMS Biophys. 2017;4:337-361. doi: 10.3934/biophy.2017.3.337.

17. Bjordal JM, Lopes-Martins RA, Iversen VV. A randomised, placebo controlled trial of low

level laser therapy for activated Achilles tendinitis with microdialysis measurement of

peritendinous prostaglandin E2 concentrations. Br J Sports Med. 2006;40:76-80;

discussion 76-80. doi: 10.1136/bjsm.2005.020842.

18. Tumilty S, Mcdonough S, Hurley DA, Baxter GD. Clinical effectiveness of low-level laser

therapy as an adjunct to eccentric exercise for the treatment of Achilles' tendinopathy: a

randomized controlled trial. Arch Phys Med Rehabil. 2012;93:733-739.

doi: 10.1016/j.apmr.2011.08.049.

19. Doyle AT, Lauber C, Sabine K. The Effects of Low-Level Laser Therapy on Pain

Associated With Tendinopathy: A Critically Appraised Topic. J Sport Rehabil. 2016;25:83-

90. doi: 10-1123/jsr.2014-0219.

20. Martimbianco ALC, Ferreira RES, Latorraca COC, Bussadori SK, Pacheco RL, Riera R.

Photobiomodulation with low-level laser therapy for treating Achilles tendinopathy: a

systematic review and meta-analysis. Clin Rehabil. 2020;34:713-722.

doi: 10.1177/0269215520912820.

21. Stergioulas A. Effects of low-level laser and plyometric exercises in the treatment of lateral

epicondylitis. Photomed Laser Surg. 2007;25:205-213. doi: 10.1089/pho.2007.2041.

22. Stergioulas A, Stergioula M, Aarskog R, Lopes-Martins RA, Bjordal JM. Effects of low-level

laser therapy and eccentric exercises in the treatment of recreational athletes with chronic

achilles tendinopathy. Am J Sports Med. 2008;36:881-887.

doi: 10.1177/0363546507312165.

23. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for

systematic reviews and meta-analyses: the PRISMA statement. PLoS Med.

2009;6:e1000097. doi: 10.1371/journal.pmed.1000097.

BJMB! ! ! ! ! !!!!!!!!Systematic Review and Meta-Analysis

Brazilian(Journal(of(Motor(Behavior(

(

Rocha et al.

2022

VOL.16

N.3

https://doi.org/10.20338/bjmb.v16i3.293

237 of 239

237 of 235

24. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane

Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

doi: 10.1136/bmj.d5928.

25. De Morton NA. The PEDro scale is a valid measure of the methodological quality of clinical

trials: a demographic study. Aust J Physiother. 2009;55:129-133.

doi: 10.1016/s0004-9514(09)70043-1.

26. Cashin AG, Mcauley JH. Clinimetrics: Physiotherapy Evidence Database (PEDro) Scale. J

Physiother. 2020;66:59. doi: 10.1016/j.jphys.2019.08.005.

27. Hume P, Hopkins W, Rome K, Maulder P, Coyle G, Nigg B. Effectiveness of foot orthoses

for treatment and prevention of lower limb injuries: a review. Sports Med. 2008;38:759-

779. doi: 10.2165/00007256-200838090-00005.

28. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-

analyses. BMJ. 2003;327:557-560. doi: 10.1136/bmj.327.7414.557.

29. Schunemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R, Vist GE, et al. Grading

quality of evidence and strength of recommendations for diagnostic tests and strategies.

BMJ. 2008;336:1106-1110. doi: 10.1136/bmj.39500.677199.AE.

30. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE

guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401-406.

doi: 10.1016/j.jclinepi.2010.07.015.

31. Ammendolia A, Cespites M, Iocco M. Topical use of aloe gel and low-level laser therapy in

overuse tendinitis of elite volleyball players: a randomized controlled trial. Sport Sci Health.

2016;12:209-213. doi: 10.1007/s11332-016-0276-y.

32. Tumilty S, Mani R, Baxter GD. Photobiomodulation and eccentric exercise for Achilles

tendinopathy: a randomized controlled trial. Lasers Med Sci. 2016;31:127-135.

doi: 10.1007/s10103-015-1840-4.

33. Geremia JM, Baroni BM, Bobbert MF, Bini RR, Lanferdini FJ, Vaz MA. Effects of high

loading by eccentric triceps surae training on Achilles tendon properties in humans. Eur J

Appl Physiol. 2018;118:1725-1736. doi: 10.1007/s00421-018-3904-1.

34. Martin RL, Chimenti R, Cuddeford T, Houck J, Matheson JW, Mcdonough CM, et al.

Achilles Pain, Stiffness, and Muscle Power Deficits: Midportion Achilles Tendinopathy

Revision 2018. J Orthop Sports Phys Ther. 2018;48:A1-A38.

doi: 10.2519/jospt.2018.0302.

35. Bjordal JM. Low level laser therapy (LLLT) and World Association for Laser Therapy

(WALT) dosage recommendations. Photomed Laser Surg. 2012;30:61-62.

doi: 10.1089/pho.2012.9893.

36. Jenkins PA, Carroll JD. How to report low-level laser therapy (LLLT)/photomedicine dose

and beam parameters in clinical and laboratory studies. Photomed Laser Surg.

2011;29:785-787. doi: 10.1089/pho.2011.9895

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Citation: Rocha ES, Machado E, Sonda FC, Pompeo KD, Santos PF, Scheeren MB, Geremia JM, Vaz MA. (2022).!

Photobiomodulation effects on achilles tendon pain: a systematic review and meta-analysis of randomized clinical

trials. Brazilian Journal of Motor Behavior, 16(3):222-239.

Editor-in-chief: Dr Fabio Augusto Barbieri - São Paulo State University (UNESP), Bauru, SP, Brazil. !

Associate editors: Dr José Angelo Barela - São Paulo State University (UNESP), Rio Claro, SP, Brazil; Dr Natalia

Madalena Rinaldi - Federal University of Espírito Santo (UFES), Vitória, ES, Brazil; Dr Renato de Moraes – University

of São Paulo (USP), Ribeirão Preto, SP, Brazil.!

open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives

4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the

original author and source are credited.

Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior –

CAPES-Brasil - Finance Code 001. ESR, FCS and KDP were supported by CAPES-Brasil with PhD scholarships. EM

was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq-Brasil, with an

undergraduate research scholarship. MAV receives a research grant from CNPq-Brasil not related to this study.

Competing interests: The authors have declared that no competing interests exist.

DOI:!https://doi.org/10.20338/bjmb.v16i3.293