Moshfeghinia et al.

BMC Neurology (2023) 23:395 BMC Neurology

https://doi.org/10.1186/s12883-023-03445-7

RESEARCH Open Access

The effects of transcranial direct-current

stimulation (tDCS) on pain intensity of patients
with fibromyalgia: a systematic review
and meta-analysis
Reza Moshfeghinia1,2, Dorsa Shekouh1,2, Sara Mostafavi1,2, Mehrnaz Hosseinzadeh3, Amir Reza Bahadori1,2,
Saeed Abdollahifard2,4 and Ali Razmkon2*

Abstract
Introduction Fibromyalgia (FM) is a chronic pain condition that affects millions of people worldwide. Transcranial
Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that has shown promise as a potential
treatment for FM by modulating pain perception and reducing symptoms, such as fatigue and depression. We aimed
to systematically review studies that assess the effect of tDCS on pain reduction in FM patients.
Methods Seven electronic databases (PubMed, Scopus, Embase, PsycINFO, Web of Science, Cochrane, and CINAHL
Complete) were searched for records in English. Studies that measured the effect of tDCS on pain intensity in FM
patients were included. The Cochrane Collaboration’s tool was used to assess the quality of the included studies.
A random-effect model was preferred, and statistical analysis was performed by Stata software version 17.
Results Twenty studies were included for qualitative, and eleven for quantitative analysis. Out of 664 patients
included in the study, 443 were in the stimulation group. The left M1 area was the most common stimulation target
(n = 12), and 2 mA was the most common stimulation amplitude (n = 19). The analysis showed that active tDCS signifi-
cantly reduced pain intensity in FM patients in comparison to the sham group (SMD= -1.55; 95% CI -2.10, -0.99); also,
no publication bias was noted.
Conclusion Our systematic review highlights the potential effect of tDCS on the reduction of pain intensity in FM
patients. Additionally, this current evidence could suggest that tDCS applied at an intensity of 2mA to the left M1
is the most effective strategy.
Keywords Fibromyalgia, tDCS, Pain, Transcranial Direct Current Stimulation, Noninvasive brain stimulation

*Correspondence:
Ali Razmkon
Ali.razmkon@gmail.com
Full list of author information is available at the end of the article

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 2 of 22

Introduction with FM [13]. A recent meta-analysis by Teixeira et al.

Fibromyalgia (FM) is a heterogeneous, long-lasting dis- included 16 RCTs that encompassed 26 different tDCS
order that mostly presents with widespread musculoskel- protocols and confirmed the overall analgesic effect of
etal pain [1]. The prevalence of FM varies across different the intervention and the effectiveness of targeting both
regions and populations, but the global average is esti- M1 and DLPFC [14].
mated to be around 2.7% [2]. Due to the debilitating pain Previous meta-analyses and systematic reviews indi-
and concomitant symptoms such as fatigue and cogni- cated that tDCS is useful for reducing pain intensity in
tive impairments, FM impairs psychological, physical, FM patients. However, previous studies showed that the
and social functioning; therefore, it may result in mental impact of tDCS depends on the location of its anodal
health issues for affected individuals [3, 4]. Various inter- placement, amplitude, the duration of each session, fre-
ventions, such as exercises, cognitive-behavior therapy quency, and other variables. Therefore, we decided to
(CBT), medications, and neuromodulation, have been update previous meta-analyses to gain a better under-
proposed for the treatment of FM. Both pharmacologi- standing of the effect of tDCS on the pain intensity of FM
cal and non-pharmacological treatments can help relieve patients and the optimal protocol.
pain in FM patients [5]. Pharmaceutical treatment is
used widely owing to availability and accessibility; how- Methods
ever, it only relieves the patients’ condition and does not To establish the effects of transcranial direct current
cure FM [6–8]. Some of the common medications that stimulation on pain intensity perception in patients with
are prescribed to reduce the symptoms of patients are FM, this systematic review and meta-analysis were con-
gamma-aminobutyric acid A agonists, Benzodiazepines, ducted according to the Preferred Reporting Items for
selective serotonin reuptake inhibitors (SSRI), and ser- Systematic Reviews and Meta-analysis (PRISMA) guide-
otonin-norepinephrine reuptake inhibitors (SNRI). In lines for 2020 [15]. The study protocol was registered
addition to therapeutic effects, the aforementioned phar- in the International prospective register of systematic
maceutical drugs may have many side effects such as reviews (PROSPERO) with the following registration
erectile dysfunction, dizziness, gastrointestinal discom- number: CRD42022383060.
fort, and tiredness [6].
Although there is no clear understanding of the dis- Search strategy
ease’s etiology, the consensus on its pathogenesis is dys- Seven electronic databases (PubMed, Scopus, Embase,
functions in the central processing of pain perception PsycINFO, Web of Science, CINAHL Complete, and
and control systems that result in a state of increased Cochrane) were searched for English records up to June
sensitization to pain and other stimuli [9]. One possible 2022. Searches were performed using combinations of
way of ameliorating the FM symptoms may be to modu- the following keywords: “Fibromyalgia” OR “Fibrosi-
late the activity of brain areas involved in pain percep- tis” AND “Transcranial Direct-Current Stimulation”
tion and control mechanisms through non-invasive brain OR “tDCS”. The search didn’t limit the above words or
stimulation techniques. Neuromodulation, especially any synonyms included in the search strategy. Detailed
transcranial direct current stimulation (tDCS), has been search strategies for each database are accessible in Sup-
shown to have a remarkable impact on pain relief and plementary Materials Part B. The references of included
functional improvement of FM patients in many studies studies were also screened to identify potentially eligible
[6, 10, 11]. Furthermore, the efficacy of tDCS in various articles.
psychological conditions such as depression, tinnitus,
and pain reduction has been demonstrated and might Eligibility criteria
be effective for reducing the symptoms of patients with We included clinical trial studies that investigated the
FM [6, 8, 10]. However, the results have been inconsist- effect of tDCS on the pain intensity of FM in humans
ent and heterogeneous, making it difficult to draw defini- older than 18 years with symptoms lasting more than 3
tive conclusions about the efficacy and optimal protocol months. The following studies were excluded: (1) stud-
of tDCS for FM. A systematic review and meta-analysis ies that examined pain in conditions other than FM;
by Hou et al. reviewed 5 articles on the effect of tDCS on (2) studies with insufficient data to calculate the effect of
FM and found a significant result supporting its analgesic tDCS on pain intensity in FM patients; (3) duplicate stud-
effects but with a smaller effect size than rTMS. They also ies or studies with overlapping participants; (4) obser-
found no substantial difference in effect size between M1 vational studies, reviews, editorials, conference papers,
and DLPFC as target sites [12]. However, Zhu et al. found case series/reports with fewer than 10 cases, and animal
M1 as the effective target area but did not confirm the experiments; (6) qualitative designs. Also, for the meta-
role of DLPFC stimulation in pain reduction of patients analysis, studies without control or placebo groups were
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 3 of 22

excluded. Studies were identified by two investigators model was used to pool the extracted unstandardized
(DSh and SM) independently according to the above cri- difference in means and the corresponding confidence
teria, while discrepancies were resolved by consensus or intervals of the studies. Heterogeneity among the studies
with a third investigator (RM or SA). was assessed using the chi-squared test and I2 statistic.
To assess the risk of publication bias, we employed two
Study selection statistical tests: Egger’s test and Begg’s test. These tests
Two authors (DSh and SM) independently screened the examine the relationship between the effect size and the
titles and the abstracts of the potentially eligible studies standard error or the sample size of each study and pro-
using EndNote software version 20. They applied the pre- vide a p-value to indicate the significance of the asym-
defined inclusion and exclusion criteria to select the stud- metry. To visualize the publication bias, a funnel plot was
ies for full-text assessment. The full texts of the selected utilized, plotting the effect size against the standard error
studies were retrieved and evaluated independently for each study. A symmetrical funnel-shaped distribu-
by the same authors. Any conflicts related to the study tion of the studies suggests a low risk of publication bias,
design or methods, and the final decision of including while an asymmetrical distribution suggests a high risk
or excluding studies, were resolved by two other authors of publication bias. Subgroup analysis was performed to
(RM and SA). At all these stages, a functional neurosur- estimate the pooled effect in the target population, type
geon (AR) was consulted if necessary. The number of of the study, pain assessment tools, current intensity,
studies that were included and excluded at each stage was electrode site, and sex subgroups. A sensitivity analysis
recorded and reported in a PRISMA flow diagram. was also conducted to test the robustness of the pooled
effect size. All analyses were conducted in Stata software
Data extraction (version 17, Stata Corporation, College Station, Texas,
Two authors (DSh and SM) separately extracted the USA). P-values less than 0.05 were considered statisti-
information from included articles. Disagreements were cally significant.
resolved by discussing the controversies with a third
author (SA). The following general characteristics were Results
collected from each study: First author, publication year, Selection of studies
country, study type, sample size, target areas and elec- Figure 1 depicts the PRISMA flow diagram. The search
trode positions, tDCS protocol (intensity, session dura- criteria initially yielded 471 articles from the databases
tion, number of sessions, and duration of intervention based on the proposed keywords. EndNote automatically
(wks)), control condition, associated interventions, and removed 270 duplicates, and 159 articles were subse-
pain intensity outcome measurement. quently excluded after screening the titles and abstracts.
Consequently, 42 articles were included in this screen-
Risk of bias assessment ing step. Following full-text evaluation, 22 articles were
We assessed the risk of bias of included studies with excluded, ultimately leaving 20 studies for qualitative
the risk of bias assessment tool of the Cochrane Col- analysis and 11 studies for quantitative analysis.
laboration [16]. Two reviewers (DSh and SM) indepen-
dently assessed the risk of bias in the studies. Studies Study characteristics
were judged individually as three grades: ‘low risk’ was We included 16 RCTs and four crossover studies, with a
assigned if the study addressed risks well because the total of 664 participants. Of those, 443 were in the active
study design was clarified, ‘unknown risk’ was assigned if stimulation group. The studies used anodal tDCS with
it retained risks because details were not stated suitably, different intensities, electrode positions, and stimulation
and ‘high risk’ was allocated if there were serious risks durations: Anodal tDCS was administered at an intensity
that could affect the study outcome due to biased study of 2 mA for 17 studies [6, 8, 18–32], 1.5 mA for 2 stud-
design. If an agreement could not be reached, a third ies [6, 33], and 1 mA for 2 studies [34, 35]. The locations
reviewer (RM or SA) acted as an arbiter. of the target electrode were the left primary motor cor-
tex (M1, corresponding to C3) with an anode over the
Quantitative analysis left M1 [8, 18, 19, 21, 22, 25, 26, 28–30, 32, 34], an anode
The mean changes and standard deviation (SD) of pain over left C2 [33], anode over right C2 [24], an anode over
intensity in the tDCS and Sham groups were used to left DLPFC [21, 23, 27, 28, 31–33, 35], an anode over the
obtain the overall effect size (standardized mean differ- right occipital nerves [6], an anode over SO [19, 20], an
ence (SMD)). We also calculated SD using the standard cathode over SO [19], cathode over M1 [19]. In all stud-
error (SE) and 95% confidence interval (CI) through a ies except one [31], stimulation was applied for 20 min,
method described by Hozo et al. [17]. A random-effects although the number of sessions mostly varied from 1
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 4 of 22

Fig. 1 PRISMA flowchart of the included studies

to 10, except for 2 studies, one of which used 20 sessions treatment of FM pain. Kang et al. [29] found that add-
[23], and the other was a home-based study that applied ing pharmacotherapy (Pregabalin or Duloxetine) to
the stimulation for 20–60 sessions [31], with a mean tDCS over M1 enhanced the analgesic effect compared
of 6.68 sessions (excluding the study with 20–60 ses- to tDCS alone or pharmacotherapy alone. Silva et al.
sions). For assessing pain intensity during the interven- [35] reported that adding a Go/No-go task to tDCS over
tion, the studies used different scales. Four studies used DLPFC improved attention and pain in FM patients, sug-
the Numeric Rating Scale (NRS) [6, 18, 24, 33], 2 stud- gesting a possible role of cognitive modulation. Yoo et al.
ies assessed pain using the Visual Analogue Scale (VAS) [6] showed that adding prefrontal tDCS before occipital
[8, 19–22, 25–32, 34], and the Pain Catastrophizing Scale nerve stimulation (ONS) increased pain relief and quality
(PCS) was used in two of them [23, 35] (Table 1). of life in FM patients who did not respond to ONS alone.
Mendonca et al. [20] demonstrated that adding aerobic
Side effects exercise (AE) to tDCS over M1 reduced pain intensity
We assessed the reported adverse effects of tDCS, and and improved mood and anxiety in FM patients, indicat-
most of the studies reported no significant or only mild ing a synergistic effect of both interventions. These stud-
adverse effects; tingling or itching were the most com- ies suggest that combining tDCS with other interventions
mon. Six studies [19, 24, 26, 29, 31, 32] reported the may optimize the analgesic responses in FM, but further
severity of side effects as major; the mentioned major research is needed to compare the efficacy and safety of
side effects were skin redness [18, 23, 30], sleepiness [18, these different strategies.
28], tingling [18, 23, 25], burning [23], headache [28], and
itching [32]. Five studies reported mild side effects, such New approaches
as skin redness [20, 21], tingling [21, 22, 35], itching [22, Two studies [22, 31] employed modifications to conven-
35], dizziness [29], light headache [29], transient sleep tional tDCS interventions that demonstrated significant
disturbances [29], and burning [35]. effects in reducing pain intensity when compared to sham
groups. Villamer et al. [22] applied high-definition tran-
Second intervention scranial direct current stimulation (HD-tDCS) to offer
Four of the included studies have investigated the a more precise and focused method of stimulation for a
effects of adding a second intervention to tDCS for the single session. Brietzke et al. [31] utilized home-based
Table 1 Characteristics of all included studies
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

qualitative
Roizenblatt Brazil RCT​ 11 (f ) M1 Right SO Anodal, None None VAS Aim: to investi-
et al., 2007 11 (f ) Left DLPFC 2 mA, gate the effect
[32] 20 min, of tDCS-induced
Moshfeghinia et al. BMC Neurology

5 sessions pain reduction

in consecu- on sleep structure
tive days in FM
10 sham Turned Result: tDCS
(f ) off after 30 s stimulation can
of stimulation decrease pain
only in M1 condi-
(2023) 23:395

tion, and tDCS

can change
sleep structure,
specific to the site
of stimulation.
Duration of effect:
NA
Silva et al., Brazil RCT, cross- 17/20 18/20 Left DLPFC Right SO Anodal, 1 mA, Go/No-go task Minor: tingling, HPTh, HPTo, Aim: Anodal
2017 [35] over design (f ) (f ) 20 min, burning, and itch- tDCS over the left
Single session ing. In both con- DLPFC modu-
ditions lates attention
and pain in fibro-
myalgia
Result: active
stimulation
increased HPTh
and HPTo
Duration: NA
Mendonca Brazil RCT​ 30 - f/m 15 (AE group) Left M1 Right SO Anodal, 2 mA, AE on a tread- Mild adverse VNS Aim: to assess
et al., 2016 (tDCS/AE 20 min, mill, 40 min, 9 effects, the effect of com-
[20] group (n = 15), 5 sessions, sessions over 4 not different bined interven-
tDCS group consecu- weeks between groups. tion of tDCS
(n = 15)) tive days and AE on pain
over the first in FM
week. Result: the combi-
nation interven-
tion is superior
in pain reduction
compared to indi-
vidual treatments.
Duration of effect:
after one month
of intervention.
Page 5 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

De Ridder Belgium RCT, crosso- 19 19 matched Right Occipi- Left OCF (C2 Anodal, 1.5 None None NRS, PCS Aim: to inves-
et al., 2017 ver design healthy con- tal nerve field dermatome) mA, 20 min, tigate
[24] trol (Crossover (OCF) 3 sessions, the mechanisms
design, 2 every behind the effect
weeks wash- two days, of OCF on pain
Moshfeghinia et al. BMC Neurology

out period over a week in FM.

between con- Result: active
ditions) Sham tDCS shows
significant pain
reduction com-
pared to sham
(2023) 23:395

and baseline.
Duration
of effects: NA
Brietzke Brazil RCT​ 10 (f ) 10 (f ) Left DLPFC Right DLPFC Anodal, None/ bifrontal Mild and tran- VAS (global Aim: To test
et al., 2020 2 mA, 30 min, HB-tDCS sient: headache, pain in last the effective-
[31] 60 sessions itching, tingling, 24 h), B-PCP:S, ness of HB-tDCS
over 12 weeks and local redness PPT, HPTo, over DLPFC
(5 consecu- in multiple ses-
tive days min- sions on daily
imum interval pain scores.
of 16 h) Result: tDCS
was superior
to the sham
group alone
in reducing
pain intensity.
Levels of BDNF
predicted better
response
Duration of effect:
NA
Page 6 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

Kang et al., South Korea RCT​ 46 No sham Left M1 Right SO Anodal, 2 pharmaco- No serious VAS Aim: to investi-
2020 [29] group mA, 20 min, therapy adverse effect gate the effects
5 sessions, was reported. of add-on tDCS
consecutive stimulation
days. on pain in FM.
Moshfeghinia et al. BMC Neurology

Result: tDCS
is effective
in pain reduc-
tion and other
features in FM.
Duration
(2023) 23:395

of effects:
after one month
post-stimulation.
Forogh Iran RCT​ 15 (f ) No sham Left DLPFC Right SO Anodal, None None VAS Aim: to com-
et al., 2021 group 2 mA, 20 min, pare the effects
[27] 3 sessions, of rTMS and tDCS
over one on pain and qual-
week (every ity of life in FM
other day) Result: pain
intensity was sig-
nificantly reduced
in both groups,
however, rTMS
was more effec-
tive.
Duration of effect:
just after course
termination
Page 7 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

EL-Badawy Egypt RCT​ 15 No sham Left M1 Right SO Anodal, 2 None Local tingling, VAS Aim: to compare
et al., 2021 group – mA, 20 min, 8 well-tolerated the efficacy
[25] but the TMS sessions, complaint of rTMS and tDCS
group of headache in pain reduction
Moshfeghinia et al. BMC Neurology

with n = 15 and dizziness in FM

was examined Result: both inter-
ventions were sig-
nificantly efficient
in pain reduction
significantly,
however, rTMS
(2023) 23:395

resulted in better
improvement.
Duration
of effects:
Caumo Brazil RCT​ 24 (f ) 24 (f ) Left DLPFC Right DLPFC Anodal, 2 mA, None/ bifrontal Severe: burning VAS, PCS, FIQ Aim: to evalu-
et al., 2022 20 min HB- tDCS sensation, ate the efficacy
[23] Mild: tingling, and safety
redness, head- of home-based
ache, neck pain, bifrontal tDCS
mood swings, in reducing pain
concentration and disability due
difficulties to pain in FM
Result: positive
effect
Duration
of effects: NA
quantitative
Fregni et al., Brazil RCT​ None Mild, simi- VAS Same as study
2006 [28] lar to sham: subjects
Sleepiness in the Roizenblatt
and headache et al. study
were the most Result: tDCS
frequent stimulation of M1
had significant
pain reduction
in FM compared
to DLPF and sham
group
Duration of effect:
at least 3 weeks
after stimulation
Page 8 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

Valle et al., Brazil RCT​ 14 (f ) M1 Contralateral 2 mA, None Minor VAS Aim: to investi-
2009 [21] SO 20 min, and uncommon: gate the effect
13 (f ) DLPFC 10 sessions, tingling, skin of tDCS
consecutive redness. Same stimulation of M1
14 (f ) Sham (M1)
days with the sham and DLPFC on FM
Moshfeghinia et al. BMC Neurology

group Result: M1 stimu-

lation markedly
decreases pain
in FM but no evi-
dence for the effi-
cacy of DLPFC
(2023) 23:395

stimulation
Duration of effect:
M1 stimulation
reduces pain
that persists
for up to 2
months.
Mendonca Brazil, RCT​ 6 Right SO Left M1 Cathodal, None Mild tingling VNS, PPT, total Aim: to deter-
et al., 2011 6 Left M1 Right SO 2 mA, 20 min at the beginning, body area mine the efficacy
[19] no side effects of pain of tDCS with dif-
6 Left M1 Right SO Anodal, 2 mA, ferent active elec-
6 Right SO Left M1 20 min trode positions
6 Left M1 Right SO Sham, current on pain reduction
on only for in FM
the initial 30 s Result: SO tDCS
resulted
in a significant
pain reduction
both as cathode
and anode
Duration
of effects: NA
Page 9 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

Villamar USA RCT, crosso- 16/18 Crossover Left M1 Anodal, 2 None /HD-tDCS Mild to moder- VNS, PPT, Aim: short term
et al., 2013 ver design design, par- mA, 20 min, 1 ate tingling and others effects of HD-
[22] ticipants have session or itching dur- tDCS on pain
3 different ing both active reduction in FM
interventions Cathodal, 2 and sham Results:
Moshfeghinia et al. BMC Neurology

with 7 days mA, 20 min, 3 stimulation, Immediately

interval sessions which resolved after stimulation
sham over a few only cathodal HD-
minutes tDCS was effec-
tive and 30 min
after stimulation
(2023) 23:395

both active
interventions
resulted in better
pain reduction
than the sham.
Duration
of effects: NA
Foerster USA RCT, crosso- 12 (f ) Crossover Left M1 Right SO Active None None VAS Aim: To investi-
et al., 2015 ver design design, 7 Anodal, 2mA, gate the effects
[26] days washout 20 min, 5 of tDCS on brain
period consecutive metabolites
between con- days and the predictive
ditions sham value of treat-
ment efficacy
in FM.
Result: tDCS
reduced pain
intensity. tDCS
also have effects
on the brain
metabolites.
Baseline levels
of these metabo-
lites predicted
pain reduction
after tDCS.
Duration
of effects: NA
Page 10 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

Fagerlund Norway RCT​ 24 24 Left M1 Right SO Anodal, 2 None Skin redness, VAS, PPT Aim: to investi-
et al., 2015 mA, 20 min, sleepiness, gate the effect
[18] 5 sessions, and tingling were of tDCS stimula-
consecutive reported same tion on pain in FM
days in the active Result: tDCS
Moshfeghinia et al. BMC Neurology

and sham group. has a small

Acute mood but significant
changes were effect on pain
more reported reduction
in the sham in FM.Duration
group of effects: NA
(2023) 23:395

Junior et al., Brazil RCT​ 10 (f ) 10 (f ) Left M1 Right SO Anodal, 1 None None VAS Aim: to evaluate
2015 [34] mA, 20 min, the effect of tDCS
10 sessions, on pain and qual-
consecutive ity of life in FM.
days. Result: tDCS
is effective in pain
control of FM.
patients
Duration
of effects: NA
Yoo et al., Belgium RCT​ 20 Left Right SO 1.5 mA, ONS Tingling and itch- NRS Aim: to investi-
2018 [6] DLPFC + ONS 20 min, each ing gate the effect
20 ONS alone intervention, of adding
8 sessions prefrontal tDCS
20 over 4 weeks, before ONS
sessions were on pain and qual-
3 days apart. ity of life in FM.
Results: pre-
frontal tDCS
did not change
the pain com-
pared to ONS-
only group.
Duration
of effects: NA
Page 11 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

To et al., Belgium RCT​ 11 Left DLPFC Right DLPFC Anodal, 1.5 None None NRS, PCS Aim: to com-
2017 [33] mA, 20 min, 8 pare the effects
15 Left occipital Right occipi- sessions, in 4 of bifrontal
tal weeks and occipital
tDCS on pain
Moshfeghinia et al. BMC Neurology

16 Initial 10 s and fatigue in FM

of active Result:
stimulation both bifrontal
and then and occipi-
inactive tal tDCS
for 20 min, reduced pain
(2023) 23:395

same number scores, DLPFC

of sessions. also improved
fatigue and pro-
vided more gen-
eral relief than C2
stimulation
Duration
of effects: NA
Khedr et al., Egypt RCT​ 18 18 Left M1 Right SO Anodal, 2 None Itching and red- VAS Aim: to evalu-
2017 [30] mA, 20 min, ness of skin ate the effects
10 sessions, 5 in only 3 cases of tDCS on pain,
consecutive from the active mood, and serum
days over two group. endorphin levels
weeks. in the treatment
of FM.
Results: M1-tDCS
was able
to improve
pain in FM
significantly. This
effect is related
to changes
in serum endor-
phin levels
Duration
of effects: at least
one month
after stimulation
Page 12 of 22
Table 1 (continued)
Author, country design Active group Sham group active Cathode tDCS Associated Side effects Pain Notes (aim,
publication (n) (n) electrode location protocol interventions/ outcome result, duration
year location form of tDCS used of effects last)

Melo et al., Brazil RCT​ 11 (f ) Left M1 Right SO Anodal, 2 None None VAS Aim of study:
2020 [8] mA, 20 min, To compare
1 week (5 the effects of two
consecutive tDCS protocols
days) on pain and EEG
alpha-2 oscilla-
Moshfeghinia et al. BMC Neurology

9 (f ) Anodal, 2 tions in FM
mA, 20 min, Result: Both pro-
2 weeks (10 tocols reduced
consecutive pain intensity
days exclud- without signifi-
ing week- cant difference,
ends)
(2023) 23:395

but only those

received for 5
11
consecutive days,
(f ) − 5 con-
showed a sig-
secutive days
nificant reduction
in alpha-2 power
in the frontal
and parietal
region
Duration
of effects: NA
Abbreviations: HPTh Heat pain threshold, HPTo Heat pain tolerance, DLPFC, SO Supraorbital, VAS Visual analog scale, FIQ Fibromyalgia impact questionnaire, B-PCP:S Brazilian Portuguese version of the profile of chronic
pain: screen, PPT Pain pressure threshold, HB-tDCS home-based tDCS, CIRS Cumulative illness rating scale, VNS Visual numerical scale, DASS-21 Depression anxiety stress scale-21, AE Aerobic exercise, ONS Occipital nerve
stimulation, PCS Pain catastrophizing scale
Page 13 of 22
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 14 of 22

tDCS as a novel approach, which monitored treatment trim-and-fill method, which ultimately revealed no evi-
adherence by recording impedance, time of use, and cur- dence of publication bias.
rent flow.
Subgroup analysis
Synthesis of results Subgroup analyses were conducted based on variations
Overall analysis in research design, the pain assessment tool employed,
We conducted a meta-analysis of 11 studies [6, 8, 18, the number of tDCS sessions administered, current
19, 21, 22, 26, 28, 30, 33, 34] with a total sample size of intensity, electrode placement, and gender. The analy-
414 subjects to compare the effects of tDCS and control sis, as depicted in Table 2, revealed an improvement in
interventions on pain intensity in patients with fibromy- pain scores across both types of included study designs,
algia. We aggregated 22 effect sizes and determined that namely randomized controlled trials (RCT) (SMD =
tDCS significantly reduced pain intensity compared to -1.70, 95% CI [-2.97, -0.42]) and crossover studies (SMD
controls (SMD = -1.65; 95% CI -2.67 to -0.63). However, = -1.55, 95% CI [-2.10, -0.99]), with no statistically sig-
we also identified significant heterogeneity (I2 = 94.16%) nificant difference observed (p = 0.83). Upon further
among the studies (see Fig. 2). Therefore, we conducted examination, the analysis stratified by the pain assess-
subgroup analysis to investigate potential sources of het- ment measurement tools demonstrated a significant
erogeneity (please refer to Supplementary Material Part disparity in pain scores when utilizing the Visual Analog
A, Figs. 1, 2, 3, 4, 5 and 6). Scale (VAS) (SMD = -1.97, 95% CI [-3.53, -0.41]) and
the Numeric Rating Scale (NRS) (SMD = -1.18, 95% CI
Risk of bias within studies [-2.11, -0.25]), yet no significant distinction between the
We assessed the quality and risk of bias of the included two tools was evident. Likewise, the subgroups involving
studies using the Cochrane risk-of-bias tool. Random the primary motor cortex (M1) (SMD = -1.13, 95% CI
sequence generation (selection bias) was low in 15 stud- [-2.75, 0.49]) and dorsolateral prefrontal cortex (DLPFC)
ies, two had a high risk, and three had an unclear risk. (SMD = -4.19, 95% CI [-9.01, 0.63]) exhibited a signifi-
Allocation concealment (selection bias) was deemed low cant effect in reducing pain, with no discernible varia-
in 11, high in four, and unclear in five studies. Perfor- tion between them. Regarding current intensity, both 2
mance bias and detection bias were reported as high in mA (SMD = -1.55, 95% CI [-2.97, -0.13]) and less than 2
three and six studies, respectively. On average, the quality mA (SMD = -1.88, 95% CI [-2.67, -1.19]) were associated
assessments indicated that the studies had a low risk of with lower pain scores. Furthermore, an analysis based
bias (Figs. 3 and 4). on gender revealed a noteworthy reduction in pain fol-
lowing intervention in both male and female groups, as
Sensitivity analysis and publication bias well as in the female-only subgroup (SMD = -1.71, 95%
We conducted a sensitivity analysis to evaluate the indi- CI [-3.35, -0.08] and SMD = -1.29, 95% CI [-2.68, 0.10],
vidual impact of each study on the SMD, which serves as respectively). In the encompassed studies, the number
the primary outcome in our mathematical model. This of sessions varied, including 1, 5, 8, and 10 sessions, all
analysis involved the systematic removal of one study of which exhibited a significant reduction in pain. How-
at a time. The findings, depicted in Fig. 5, indicated that ever, no statistically significant distinctions were identi-
the exclusion of Khedr et al.‘s study [30] had a compara- fied among these session counts. Detailed information
tively greater influence on the estimation of the overall regarding the subgroup analyses can be found in Table 2,
effect size when compared to the other studies (effect while the forest plots are available in Supplementary
size = -1.31; 95% CI -2.16 to -0.46, p = 0.003). However, Material Part A, Figs. 1, 2, 3, 4, 5 and 6.
it is important to note that this particular study carried
a relatively low weight in the meta-analysis, accounting Discussion
for only 8.31% of the total, and as a result, its impact on The present systematic review included 20 studies, of
both the SMD and the 95% CI was limited. Addition- which 11 were eligible for quantitative analysis. Nine of
ally, we conducted an examination of publication bias these were RCTs, and two were within-subject cross-
employing Egger’s test, Begg’s test, and a funnel plot. The overs. The meta-analysis revealed that active tDCS
funnel plot displayed an asymmetric distribution of the reduced pain intensity in FM patients compared to the
data, implying the potential presence of publication bias. sham intervention. Both M1 and DLPFC, as the most
Nonetheless, this observation contradicted the outcomes frequently targeted regions in neuromodulation for pain
of Egger’s and Begg’s tests, which indicated a weak risk processing, exhibited a significant decrease in pain inten-
of publication bias (p = 0.001 and p = 0.06, respectively) sity when stimulated. M1 emerged as the most commonly
as illustrated in Fig. 6 Consequently, we conducted the targeted site in the studies; nevertheless, stimulating both
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 15 of 22

Fig. 2 Meta-analysis of the effect of anodal tDCS on pain intensity in fibromyalgia for all included studies

M1 and DLPFC proved effective in modulating pain protocols with current intensities less than 2 mA. Gender
intensity in FM. Our subgroup analysis failed to detect dependency regarding the analgesic effects of tDCS was
any differences between M1 and DLPFC. explored in a subgroup analysis, where female patients
The effect of more frequent sessions of tDCS on pri- exhibited a significant response to treatment. Neverthe-
mary outcomes was not observed in the subgroup analy- less, no significant difference was observed when male
sis. Although more frequent sessions of tDCS had the patients were included in the studies (p = 0.75).
largest effect size in reducing pain (SMD = -2.69; 95% CI Most of the included studies reported either mild side
-5.37 to -0.02, p < 0.001), the test of group difference with effects or no side effects at all. The side effects that were
less frequent sessions was not significant (p = 0.22). This most frequently reported include skin redness, sleepi-
finding contradicts the previously mentioned cumulative ness, transient sleep disturbances, itching, tingling, light
effect of tDCS on pain intensity reduction [31]. This con- headaches, and dizziness, demonstrating the safety and
troversy may exist because we primarily included studies tolerability of this procedure. However, despite the con-
that focused on short-term effects, and the longer-lasting sensus on the safety of tDCS, some studies (5 out of 20)
effects of tDCS on pain intensity in the patient popula- reported significant side effects. This necessitates further
tion need to be addressed in future studies. research to quantitatively assess the side effects and offer
Comparing the use of different pain intensity measures guidance on the cost-effectiveness of decisions in clinical
showed that NRS and VAS scales had no significant dif- settings.
ferences in depicting pain reduction in the intervention Several systematic reviews and meta-analyses have
group compared to sham (p-value < 0.001 with a stand- attempted to investigate the analgesic effect of neuro-
ardized mean difference of -2.02 for VAS and − 1.18 for modulation on chronic pain. Xiong et al. reviewed the
NRS). Subgroup analysis revealed that the current inten- current state of the art and future directions of non-
sity of 2 mA, as employed in the majority of included invasive brain stimulation (NIBS) for assisting individu-
studies (8 out of 11), effectively reduced pain in the inter- als with chronic pain. They illustrated a growing trend
vention group compared to the sham. However, there in the research field of NIBS over the last 20 years,
was no discernible group difference between 2 mA and demonstrating that Repetitive Transcranial Magnetic
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 16 of 22

Fig. 3 Risk of bias of included study. Randomized clinical trial (left) and crossover trial (right) based on authors’ judgment

Stimulation (rTMS) and tDCS are surpassing other such as neuropathic pain, fibromyalgia (FM), migraine,
neuromodulation methods, with tDCS even surpass- and low back pain [36]. Clinical and experimen-
ing rTMS. They deliberated upon the mechanisms, tal studies suggest that rTMS may reduce pain in FM
applications, and challenges associated with various patients by modulating neural pain pathways, such as
NIBS techniques and summarized the evidence from the descending inhibitory pathways and brain regions
clinical trials and meta-analyses regarding the efficacy involved in social-affective functions, such as the right
and safety of NIBS for various chronic pain conditions, temporal lobe [36]. El-Badawy et al. and Forogh et al.
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 17 of 22

Fig. 4 Risk of bias assessment based on subscales for all included studies based on authors’ judgment

Fig. 5 sensitivity plots of all included study

compared the effects of rTMS and tDCS on pain inten- Wen et al. conducted a systematic review and meta-
sity in patients with FM. They reported that both rTMS analysis to evaluate the effects of tDCS on pain, depres-
and tDCS significantly reduced pain intensity in FM sion, and anxiety symptoms in patients with chronic
patients, with the rTMS group experiencing greater pain. They included 27 randomized controlled trials with
and longer-lasting effects [25, 27]. a total of 1,015 participants who received tDCS or sham
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 18 of 22

Fig. 6 Funnel plot of all included study

stimulation for various chronic pain conditions. They efficacy of tDCS, albeit exclusively when the target region
found that tDCS was significantly more effective than was M1, as opposed to DLPFC [13]. Another study found
sham stimulation in reducing short-term pain intensity a significant effect size in pain reduction when com-
(SMD = -0.43, 95% CI = -0.75 to -0.12), short-term and paring stimulation of the M1 area to the DLPFC [41].
middle-term depression (SMD = -0.31, 95% CI = -0.47 Lloyd et al. found that tDCS was significantly superior
to -0.14, and SMD = -0.35, 95% CI = -0.58 to -0.11), and to sham in reducing pain (p-value = 0.005 with an SMD
anxiety scores (SMD = -0.36, 95% CI = -0.58 to -0.14) in of -0.5; 95% confidence interval − 0.4 to 0.62). They con-
patients with chronic pain, but longer-lasting effects were cluded that active anodal tDCS, with a current intensity
not observed [37]. of 2 mA applied to the left M1 for 20 min per session
Our findings are consistent with previous reviews and over 10 sessions, was the most effective approach for
meta-analyses, which have also reported a significant alleviating pain in FM [38]. The two most recent meta-
analgesic effect of tDCS in FM [9, 12–14, 38–41]. Hou analyses on the matter by Cheng et al. and Teixeira et al.
et al. [12] incorporated 16 studies and endeavored to reported a standardized mean difference of 0.4990 (95%
investigate the effects of rTMS and tDCS as supplemen- CI = 0.1757–0.8223, p < 0.01) and 1.22 (95% CI = 0.80–
tary treatments for FM. The study uncovered that NBS 1.65, p < 0.001), respectively, in pain reduction among FM
yielded significantly advantageous outcomes in terms of patients through the administration of tDCS.
pain reduction, alleviation of depression, mitigation of However, our review also differs from previous ones
fatigue, amelioration of sleep disturbance, and enhance- in some aspects of the methods and results. First, we
ment of general health/functionality in FM patients. included more studies in our meta-analysis because we
Additionally, the study revealed that rTMS exhibited a searched additional databases and updated the search
more pronounced effect size when compared to tDCS. until June 2022. This augmentation enhanced both the
Furthermore, within the realm of pain reduction, M1 quantity and quality of studies, thereby diminishing the
stimulation demonstrated a subtle but greater effect risk of publication bias. Second, we conducted a sub-
size than DLPFC stimulation, whereas DLPFC stimula- group analysis based on the target site of tDCS, owing
tion exhibited a subtle but greater effect size in terms of to the identification of substantial heterogeneity among
depression improvement when compared to M1 stimula- the studies. We ascertained that both M1 and DLPFC
tion. In a similar vein, Zhu et al. conducted a meta-anal- stimulation were efficacious in mitigating pain in FM
ysis encompassing a review of 6 RCTs and identified the patients, whereas some of the prior reviews failed to
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 19 of 22

Table 2 Meta-analysis of the subgroups of the included studies Another explanation is that tDCS modulates the func-
Subgroups Number of Standardized mean P-value
tional connectivity and activity of brain regions and
studies difference (95% CI) networks that are involved in pain processing and modu-
lation. tDCS stimulation lacks focality, and studies have
Type of Study
shown that the stimulation usually spreads beyond the
RCT​ 9 -1.70 (-2.97, -0.42) < 0.001
target site, thus resulting in network-wide changes [42].
Crossover study 2 -1.55 (-2.10, -0.99) 0.48
Cummiford et al. found that repetitive tDCS stimulation
Test of group differences: ­Qb (1) = 0.04, p = 0.83
of M1 will alter the resting state functional connectiv-
Pain assessment tool
ity in FM patients. The insula, anterior cingulate cor-
  VAS 7 -1.97 (-3.53, -0.41) < 0.001
tex, thalamus, and somatosensory cortex are among the
  NRS 4 -1.18 (-2.11, -0.25) < 0.001
brain regions where changes in functional connectivity
Test of group differences: ­Qb (1) = 0.73, p = 0.39 are reported. These changes might reflect neuroplasticity
Number of tDCS sessions induced by tDCS and could be explained by lasting pain
  10 sessions 4 -2.87 (-5.29, -2.88) < 0.001 relief beyond the stimulation period [43].
  8 sessions 2 -1.67 (-2.35, -0.98) 0.16 A third explanation is that tDCS interacts with the
  5 sessions 4 -0.43 (-1.59, 0.74) < 0.001 individual’s brain state, such as their mood, attention,
  1 session 2 -0.74 (-2.69, 1.20) < 0.001 motivation, cognitive load, and expectations, all of which
Test of group differences: ­Qb (3) = 5.22, p = 0.16 can influence the efficacy and outcome of tDCS on pain
Current intensity modulation [44, 45]. By combining tDCS with other
  2 mA 8 -1.55 (-2.97, -0.13) < 0.001 interventions such as aerobic exercise, cognitive-behav-
   Less than 2 mA 3 -1.88 (-2.67, -1.19) 0.18 ioral therapy, or task-oriented approaches, tDCS may
Test of group differences: ­Qb (1) = 0.17, p = 0.68 improve brain-state dependency and optimize the anal-
Electrode Position gesic effect of tDCS in FM patients [46]. These explana-
  M1 9 -1.13 (-2.75, 0.49) < 0.001 tions are not mutually exclusive and may work together
  DLPFC 3 -4.19 (-9.01, 0.63) < 0.001 to produce a cumulative analgesic effect of tDCS in FM
Test of group differences: Qb (1) = 1.39, p = 0.24 patients. However, more research is needed to confirm
Sexuality the exact mechanisms and optimal parameters of tDCS
  Only Female 6 -1.29 (-2.68, 0.10) < 0.001 for pain management in FM.
   Female & Male 6 -1.71 (-3.35, -0.08) < 0.001 Our systematic review harbors some limitations that
Test of group differences: ­Qb (1) = 0.15, p = 0.70 necessitate acknowledgment and remediation. Firstly,
Abbreviations: CI Confidence interval; RCT Randomized control trial, VAS Visual there exists a risk of bias within the included stud-
analogue scale, NRS Numeric rating scale, M1 Primary motor cortex, ies, given that a majority of them exhibited ambigu-
DLPFC Dorsolateral prefrontal cortex
ity or a high risk of bias in specific domains, notably
randomization, allocation concealment, blinding, and
detect a significant effect of DLPFC stimulation [9, 13]. incomplete outcome data. Such issues have the poten-
Third, we conducted a meta-analysis to investigate the tial to compromise the internal validity and reliability
potential factors that influence the effect size of tDCS of the studies, thereby affecting the accuracy and pre-
on pain outcomes, such as current intensity, target loca- cision of the results derived from the meta-analysis.
tion, number of sessions, study design, the subject’s gen- Secondly, the sample sizes across the included studies
der, and the pain measurement scale. We did not identify were notably diminutive, ranging from 10 to 60 partici-
any significant associations between these factors and the pants per study. This diminishment could impede sta-
outcomes. tistical power and the generalizability of the findings,
One explanation is that tDCS has neurochemical consequently augmenting heterogeneity and fostering
effects and alters the levels of neurotransmitters such as uncertainty in the results of the meta-analysis. Thirdly,
glutamate, glutamine, GABA, N-Acetyl Aspartate (NAA), the paucity of long-term follow-ups within the major-
and endorphins, all of which are implicated in pain trans- ity of studies precluded our ability to assess the durabil-
mission and modulation. Through the augmentation of ity and persistence of tDCS effects on pain outcomes.
anodal stimulation in M1 or other cerebral regions, tDCS This insufficiency could curtail the clinical relevance
may potentially amplify the secretion of inhibitory neu- and practicality of employing tDCS for managing pain
rotransmitters and endogenous opioids while diminish- in patients with fibromyalgia who require prolonged
ing the release of excitatory neurotransmitters, thereby treatment. Lastly, the variability in outcome meas-
yielding decreased pain sensitivity and increased pain ures and stimulation protocols among studies posed a
tolerance in FM patients [26, 30]. substantial challenge in the comparison and synthesis
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 20 of 22

of tDCS effects on pain outcomes. Disparate outcome documentation and rigorous characterization of side
measures might capture distinct facets of pain and effects as potential focal points for future studies con-
quality of life among fibromyalgia patients, each pos- tributing to the field.
sessing unique psychometric attributes and respon-
siveness to change. Meanwhile, dissimilar stimulation
protocols could potentially exert divergent mechanisms Conclusion
of action, impacting cortical excitability, neurotrans- tDCS is a promising and clinically sound treatment for
mission, neural networks, and brain-state dependency chronic pain conditions, such as fibromyalgia, believed
within fibromyalgia patients. Furthermore, these pro- to originate from the central nervous system (CNS).
tocols might also introduce varying safety and feasibil- However, we did not identify a superior stimulation
ity considerations. Regrettably, these aspects were not protocol in our subgroup analysis. More experimental
comprehensively investigated and reported in the exist- studies are required to investigate the fundamentals of
ing literature, rendering any conclusive determination the brain changes induced by various neurostimulation
unattainable. modalities and the brain mechanisms underlying their
In consideration of the limitations of our study, we effects, possibly by incorporating neuro-electrophysio-
acknowledge that the shortcomings of high-quality logical or neuroimaging studies in conjunction with the
research on the topic, heterogeneous study designs, the intervention. Future research should explore the poten-
lack of generalizability of mechanistic surveys, and the tial benefits of combining tDCS with other interven-
absence of investigations into long-term effects in pre- tions or modalities for fibromyalgia patients. Lastly, it
vious studies may have implications for the generaliz- is imperative to identify the most effective target sites
ability of our findings. and optimal stimulation parameters within individu-
Our systematic review bears significant implications alized treatment protocols that take into account the
for clinical practice and forthcoming research on tDCS brain-state dependency of neurostimulation modalities
for FM. Firstly, tDCS appears to constitute a viable before embarking on further large-scale randomized
and secure treatment option for FM patients, as the controlled trials.
majority of studies reported either no or mild adverse
effects alongside high adherence rates. Nonetheless, Supplementary Information
additional investigations are imperative to assess the The online version contains supplementary material available at https://​doi.​
long-term safety and tolerability of tDCS, especially in org/​10.​1186/​s12883-​023-​03445-7.
the context of home-based or self-administered proto-
Additional file 1: Part A: Subgroup analyses. Figure S1. Subgroup
cols, which may extend the cumulative exposure time. meta-analysis of the included studies for assessing the effect of transcra-
Secondly, there exists an exigency for more standard- nial Direct-Current Stimulation (tDCS) on pain intensity of Fibromyalgia
ized and individualized treatment protocols for tDCS, patients based on the type of study. Figure S2. Subgroup meta-analysis of
the included studies for assessing the effect of transcranial Direct-Current
given the marked variability in stimulation parameters Stimulation (tDCS) on pain intensity of Fibromyalgia patients based on the
and target sites observed across studies. Future inquir- pain assessment tool. Figure S3. Subgroup meta-analysis of the included
ies should employ rigorous methodologies to ascertain studies for assessing the effect of transcranial Direct-Current Stimulation
(tDCS) on pain intensity of Fibromyalgia patients based on number of
the optimal current intensity, duration, frequency, and tDCS sessions. Figure S4. Subgroup meta-analysis of the included studies
electrode montage tailored to each patient, contin- for assessing the effect of transcranial Direct-Current Stimulation (tDCS)
gent upon their pain characteristics and brain state. on pain intensity of Fibromyalgia patients based on current intensity (mA).
Figure S5. Subgroup meta-analysis of the included studies for assessing
Thirdly, tDCS may potentially yield synergistic effects the effect of transcranial Direct-Current Stimulation (tDCS) on pain inten-
when concomitantly administered with other inter- sity of Fibromyalgia patients based on electrode position (anode). Figure
ventions or modalities, such as pharmacotherapy, cog- S6. Subgroup meta-analysis of the included studies for assessing the
effect of transcranial Direct-Current Stimulation (tDCS) on pain intensity
nitive-behavioral therapy, exercise, or neurofeedback. of Fibromyalgia patients based on sexuality. Part B: Search Strategy
Furthermore, adopting a holistic approach to pain man-
agement, which takes into account the affective and
Acknowledgements
cognitive facets of pain when designing a tDCS regi- We are very grateful to Sina Zoghi for helping us in this work.
men and selecting target site(s), is poised to augment
its efficacy. As underscored in this review study, we Authors’ contributions
R.M. and S.A. initiate the concept and conduct the initial investigation. D.S.
advocate for an augmentation in sample sizes to bol- and S.M. conduct the evaluation and incorporate the findings. In addition to
ster the robustness of investigations, the exploration R.M., M.H. and A.B. are responsible for composing the initial draft. R.M. and S.A.
of longer-lasting effects of the proposed interventions undertake the analysis. Oversight throughout all stages is provided by S.A. and
A.R. The final version for publication is approved by all authors.
to address the issue of chronic pain, and a meticulous
Moshfeghinia et al. BMC Neurology (2023) 23:395 Page 21 of 22

Funding 12. Hou W-H, Wang T-Y, Kang J-H. The effects of add-on non-invasive brain
Not applicable. stimulation in fibromyalgia: a meta-analysis and meta-regression of
randomized controlled trials. Rheumatology. 2016;55(8):1507–17. https://​
Availability of data and materials doi.​org/​10.​1093/​rheum​atolo​gy/​kew205.
All information required is given in the text and supplementary materials, 13. Zhu C-E, Yu B, Zhang W, Chen W-H, Qi Q, Miao Y. Effectiveness and safety
other supplementary information can be obtained upon email from the cor- of transcranial direct current stimulation in fibromyalgia: a systematic
responding author. review and meta-analysis. J Rehabil Med. 2017;49(1):2–9.
14. Teixeira PE, Pacheco-Barrios K, Branco LC, de Melo PS, Marduy A, Caumo
W, et al. The analgesic effect of transcranial direct current stimulation in
Declarations fibromyalgia: a systematic review, meta-analysis, and meta-regression of
potential influencers of clinical effect. Neuromodulation. 2022. https://​
Competing interests doi.​org/​10.​1016/j.​neurom.​2022.​10.​044.
The authors declare no competing interests. 15. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD,
et al. The PRISMA 2020 statement: an updated guideline for reporting
Ethics approval and consent to participate systematic reviews. Syst Rev. 2021;10(1):1–11.
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ventions version. 2011;5:2011.
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Not applicable. the median, range, and the size of a sample. BMC Med Res Methodol.
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Author details 18. Fagerlund AJ, Hansen OA, Aslaksen PM. Transcranial direct current
1
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, stimulation as a treatment for patients with fibromyalgia: a randomized
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building, Zand Street, Shiraz, Iran. 3 Fasa Neuroscience Circle (FNC), Student 00000​00000​000006.
Research Committee, Fasa University of Medical Sciences, Fasa, Iran. 4 School 19. Mendonca ME, Santana MB, Baptista AF, Datta A, Bikson M, Fregni F,
of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Mendonca ME, Santana MB, Baptista AF, Datta A, Bikson M, Fregni F,
Araujo CP. Transcranial DC stimulation in fibromyalgia: optimized corti-
Received: 19 August 2023 Accepted: 22 October 2023 cal target supported by high-resolution computational models. J Pain.
2011;12(5):610–7. https://​doi.​org/​10.​1016/j.​jpain.​2010.​12.​015.
20. Mendonca ME, Simis M, Grecco LC, Battistella LR, Baptista AF, Fregni F.
Transcranial direct current stimulation combined with aerobic exercise to
optimize analgesic responses in fibromyalgia: a randomized placebo-
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