Introduction
Non-invasive brain stimulation (NIBS), particularly repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS) and transcranial direct current stimulation (tDCS), has emerged as a potential therapeutic approach for chronic musculoskeletal pain (CMP).1–3 By modulating cortical excitability and pain-related neural networks,4 NIBS may influence both sensory and cognitive-affective dimensions of pain.56 Contemporary neurobiological models, such as the triple network model, conceptualise chronic pain as a disorder of large-scale maladaptive brain network interactions involving the default mode network, salience network and central executive network.6 Alterations in the sensorimotor network, particularly in the primary motor and somatosensory cortices, have also been reported in CMP, highlighting potential targets for neuromodulation.78
Despite growing interest in NIBS, clinical efficacy and safety evidence for CMP management remains inconclusive.9–11 A major contributor to this uncertainty is substantial heterogeneity in stimulation targets and dosage parameters.12 TMS and tDCS have been reported to target multiple cortical regions implicated in pain processing, including the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), primary somatosensory cortex (S1) and dorsal anterior cingulate cortex (dACC).12–14 Moreover, comparable inconsistencies are evident in stimulation dosage, with dosage parameters varying across studies.14–18 TMS dosage depends not only on the intensity, duration, number and frequency of therapeutic pulses and the treatment interval, but also on the coil geometry, pulse waveform, intensity, frequency and number of pulses delivered.1619 The dosage of tDCS is related to current intensity, waveform and electrode size.20 Emerging evidence suggests a dose-response relationship for tDCS in knee osteoarthritis (KOA), with greater cumulative session frequency associated with superior improvements in pain, pain catastrophising, physical function and quality of life.21 Nevertheless, justification for parameter selection is frequently absent, and clinical decision-making often relies on empirical precedent rather than systematic optimisation and evidence-driven.20
Safety is another critical consideration for NIBS, given its direct neuromodulation action.20 Evidence indicates that both real and sham stimulations are typically associated with mild and transient adverse events (eg, skin irritation, nausea, fatigue and headache)2022–24; however, rare cases of seizures have been reported following rTMS treatment.20 Although international safety guidelines and clinical recommendations for TMS use in patient populations are available,25 adherence to them remains scant. For tDCS, the available adverse event data derive largely from short-term studies and are reported inconsistently.26 Importantly, methods for adverse event ascertainment are often inadequately described, limiting reliable estimation of adverse event frequency. Thus, the available literature primarily describes the adverse events that were reported rather than providing sufficient evidence to establish the safety profile of NIBS.
Overall, the safety profile of NIBS in CMP populations remains incompletely characterised.
This scoping review aimed to: (1) map stimulation targets and dosage parameters used in rTMS, TBS and tDCS for CMP; (2) summarise the rationale underpinning parameter selection; and (3) synthesise current practices for safety monitoring and adverse event reporting.
Methods
Patient and public involvement
None.
Design
This review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines27 and the Joanna Briggs Institute (JBI) methodology,28 guided by the six-stage framework proposed by Arksey and O’Malley.29 The protocol was registered on the Open Science Framework (DOI: http://doi.org/10.17605/OSF.IO/8HFBZ) and published previously.30
Phase 1: identify research questions
Through iterative team discussions and consultation with two experienced physiotherapists (YD and KY) with clinical and research experience in managing patients with KOA using rTMS and tDCS, we developed four research questions: (1) Which stimulation regions have been targeted by TMS and tDCS in previous studies? (2) What dosage parameters have been applied for? (3) Do studies provide a rationale for the selected stimulation target and dosage? and (4) How is safety reported in studies using TMS and tDCS?
Specifically, do they report safety outcomes, and if so, how are these outcomes documented?
Phase 2: identification of relevant studies
The lead author (SW) conducted the search in MEDLINE (PubMed), Scopus, Web of Science and Embase on 16 October 2025, using predefined keywords and subject headings (online supplemental table 1). The complete search strategy for each database is provided in the online supplemental search strategies file.
Phase 3: study selection
Eligibility criteria
Study population
We included studies that recruited adults diagnosed with CMP, defined as persistent or recurrent pain lasting longer than 3 months that arises from musculoskeletal tissue.31 Both primary and secondary musculoskeletal conditions were included based on the 11th revision of the International Classification of Diseases (ICD-11). We excluded studies on postoperative and viral CMP due to distinct pathophysiological mechanisms.32
Concept
We included studies that investigate NIBS modalities using TMS (including rTMS and TBS), tDCS or combinations of these modalities. To be eligible, studies were required to report at least one of the following parameters: (1) stimulation targets, such as M1, DLPFC, dACC and S1; (2) stimulation dosages; and (3) safety assessment to evaluate adverse effects or risks associated with the interventions.
For this review, stimulation dosage was operationalised as a multidimensional construct comprising three related but distinct dimensions: within-session dosage, treatment schedule and cumulative treatment exposure. Within-session dosage refers to the parameters that define the stimulation delivered during an individual session. The treatment schedule refers to the frequency and temporal distribution of sessions, including sessions per week, inter-session intervals and the overall treatment period.
Cumulative treatment exposure refers to the total stimulation received across the treatment course. For rTMS, within-session dosage included coil type, stimulation intensity, stimulation frequency, pulses per session, train structure, inter-train interval and related delivery parameters where reported; treatment schedule included session frequency, inter-session interval and treatment duration; and cumulative exposure was operationalised primarily as total pulses across the treatment course where calculable. For TBS, within-session dosage included coil type, stimulation pattern (intermittent/continuous TBS), burst parameters, stimulation intensity and pulses per session; treatment schedule included session frequency and treatment duration; and cumulative exposure was represented by total pulses where calculable.
For tDCS, within-session dosage included anode and cathode positions, electrode size, current intensity, stimulation duration and ramp-up/ramp-down time where reported; treatment schedule included session frequency, inter-session interval and treatment duration; and cumulative exposure was operationalised primarily as total stimulation time across the treatment course, with cumulative charge considered where sufficient information was available. Because no validated cross-modality dosage-equivalence framework exists for NIBS in CMP, these dimensions were summarised descriptively rather than combined into a single numerical dosage metric.
Context
We included studies conducted in any setting where the intervention was administered or supervised by healthcare professionals, such as neurologists, physiotherapists or pain specialists.
Source of evidence selection
We included only full-text English-language studies as the large majority of indexed NIBS trials in CMP are published in English. We considered a wide range of designs, including pilot and feasibility studies to full-scale randomised controlled trials (RCTs), crossover, case-control and observational studies. We also included pilot studies and protocols if full-text findings were not yet available, while excluding reviews, guidelines, expert opinions, books or chapters, editorials, letters and conference abstracts or proceedings.
RCT protocols were included only to map planned stimulation targets, dosage parameters and safety monitoring procedure; however, they were excluded from adverse event analyses because protocols describe planned procedures rather than observed adverse events.
Screening
Following deduplication in EndNote,33 two independent authors (BD and ZS) screened titles and abstracts in EndNote before conducting a full-text review. Any disagreements regarding study inclusion were resolved through discussion, and if necessary, a third author (SW) was consulted to reach a consensus.
Phase 4: data extraction
Two authors (BD and ZS) independently extracted data on study characteristics (online supplemental table 2), including: (1) publication details (authors, year of publication and study location); (2) study design; (3) participants’ details (sample size and CMP type); (4) interventions and comparators; and (5) outcome measures (key parameters assessed). We also extracted stimulation targets, rTMS coil types and rTMS and TBS dosage parameters (online supplemental tables 3 and online supplemental table 4). Similarly, we extracted the stimulation target, electrode size for tDCS, and tDCS dosage parameters (online supplemental table 5), including within-session dosage, treatment schedule and cumulative exposure where calculable.
Additionally, when a study provided a rationale or justification for dosage selection, we extracted this information along with any reported safety considerations. Discrepancies were resolved through discussion or consultation with a third author (LJ or SW).
Phase 5: collating, summarising and reporting results
We synthesised findings descriptively and presented them in tables and figures. Evidence was organised by anatomical region and pain characteristics (eg, widespread vs localised). Variability in stimulation parameters was identified using a structured synthesis strategy.
Studies were categorised by key intervention characteristics, including stimulation modality (TMS, tDCS or combined), stimulation frequency (eg, low- vs high-frequency rTMS; anodal vs cathodal tDCS) and dosage parameters (within-session dosage, treatment schedule and cumulative treatment exposure). Modality-specific cumulative exposure was reported where calculable, primarily as total pulses for rTMS and TBS and total stimulation time for tDCS. Although no universally accepted framework exists for interpreting NIBS dosage in CMP, we documented and summarised authors’ justifications (online supplemental tables 6–8).
Phase 6: consultation
Stakeholder consultations were conducted in two phases. During protocol development, two physiotherapists with expertise in CMP provided input on research questions and eligibility criteria. Preliminary findings were later reviewed by two clinical pain research experts (JM and DBA) to obtain research and clinically informed interpretations.
Results
We identified 12 385 records from four databases (figure 1). Following deduplication and exclusion of non-English studies, and title and abstract screening, 215 studies remained. After full-text review, 123 studies were included.
10 were RCT protocols in which participants had not yet received the intervention; therefore, 113 studies in which participants received NIBS comprised the denominator for all adverse event analyses. Publication trends show a gradual increase in studies on NIBS for CMP (figure 2). Output was limited before 2014, increased steadily from 2014 to 2018, and rose more sharply after 2019.
Despite a temporary decline in 2023, publications peaked in 2025, reflecting growing research interest.
Characteristics of included studies
Study characteristics are presented in online supplemental table 2. Fibromyalgia (n=49) was the most studied condition, followed by KOA (n=28), chronic low back pain (n=23) and other region-specific pain conditions (eg, myofascial pain syndrome, temporomandibular disorders, neck pain, rotator cuff tendinopathy, patellofemoral pain syndrome). Participants were adults with baseline pain severity generally in the moderate to severe range (NPRS rating of ≥4).
Most studies were RCTs (n=91), with fewer pilot or feasibility RCTs (n=7), crossover RCTs (n=4), RCT protocols (n=10), pre-post studies (n=6), cross-sectional study (n=1), case reports (n=3) and randomised sham-controlled interrupted time series design (n=1). Sample sizes ranged from 5 to 90 participants per group.
Interventions included rTMS (n=33), TBS (n=2) or tDCS (n=88), delivered either as standalone treatments or combined with adjunctive therapies such as exercise, education, cognitive-behavioural approaches or peripheral stimulation. Control conditions most often included sham stimulation, usual care, exercise alone or pharmacological comparators. Outcome measures were heterogeneous but consistently included pain intensity, condition-specific disability or impact scales, and psychosocial measures, and in some studies, neurophysiological or imaging outcomes.
Target and dosage of NIBS
Stimulation targets across NIBS modalities are summarised in figure 3 and online supplemental tables 3–5. Detailed information on stimulation dosage parameters is also provided in online supplemental tables 3–5.
Repetitive transcranial magnetic stimulation
Among the included 33 studies, two targeted more than one stimulation site.3435 The M1 was the primary rTMS target in 23 studies (69.7%), followed by the DLPFC (n=11; 33.3%), with one study targeting the S1. M1 stimulation was most frequently applied in studies of osteoarthritis, chronic low back pain and fibromyalgia, while DLPFC was frequently investigated in fibromyalgia.
Most protocols (79%, n=26) used high-frequency stimulation (typically 10 Hz) at 80–120% rest motor threshold with figure-of-eight coils, delivering 1200–3000 pulses per session. Treatment schedules varied widely, ranging from 1 to 60 sessions, typically delivered five sessions per week for 2–4 weeks. Where pulses per session and number of sessions were both reported, cumulative exposure could be characterised as total pulses across the treatment course, highlighting substantial differences between otherwise similar within-session protocols.
A small number of studies used low-frequency (1 Hz) stimulation. Approximately 27% (n=9) combined rTMS with exercise or other therapies. Detailed protocols are presented in online supplemental table 3.
Theta-burst stimulation
TBS was applied exclusively to the DLPFC, primarily in KOA and chronic low back pain populations. Protocols generally followed standard TBS paradigms, delivering 50 Hz bursts over short durations (mean~24 s per pulse).
One of the two TBS studies combined TBS with core stability exercises. Outcomes included pain intensity, disability and neurophysiological or neuroimaging measures, reflecting an interest in both clinical efficacy and underlying pain mechanisms. Detailed protocols are presented in online supplemental table 4.
Transcranial direct current stimulation
Of the included 88 studies, eight targeted more than one anode site.36–43 The most common montage was anodal stimulation over M1 with the cathode placed over the contralateral supraorbital (SO) region (n=63; 71.6%). Less common configurations targeted the DLPFC or other cortical regions. Typical tDCS protocols delivered currents of 1–2 mA for 20–30 min per session, across 1 to 60 sessions.
Most studies (65%, n=57) combined tDCS with exercise, physical therapy, education, mindfulness-based interventions or transcutaneous electrical nerve stimulation, suggesting a trend toward multimodal pain management. Outcomes were heterogeneous but consistently included pain intensity, physical function, quality of life and psychosocial outcomes. Several studies also incorporated neurophysiological, sensory or imaging measures.
Detailed targets and dosing parameters are presented in online supplemental table 5.
Rationale for specific dosage selection
Across 123 studies, NIBS dosage was most often justified by previously published evidence, established safety guidelines or precedent clinical trials, rather than individualised neurophysiological optimisation (table 1). Stimulation targets were justified in 63% of studies, while 37% provided no clear rationale. Similarly, frequency or current intensity was justified by prior evidence in approximately half of the studies (49%), whereas treatment duration and number of sessions were the least justified (67% lacking rationale).
These findings indicate that the rationale for within-session parameters was reported more consistently than the rationale for treatment schedule and cumulative exposure. Detailed dosage rationales are presented in online supplemental tables 6–8.
Similar patterns were observed across modalities: approximately 64% of rTMS and tDCS studies justified target selection, while rationales for stimulation intensity and treatment duration were inconsistently reported.
Adverse events and safety monitoring
Safety monitoring practices varied substantially across studies and stimulation modalities (table 2). Overall, 62% of studies did not clearly report the method used to monitor adverse events. Structured questionnaires, checklists or open-ended interviews were used in only 11% of studies, while other approaches included verbal questioning or spontaneous participant reports.
Explicit severity grading was reported in only 5% of studies. Detailed information on adverse event monitoring and reporting is presented in online supplemental tables 6–8.
Among studies in which participants received the intervention, reported adverse events were predominantly mild and transient (table 3). The most frequently reported adverse events in active stimulation conditions were headache (27%), local pain at the stimulation site (19%), itching (13%), skin redness or irritation (11%) and fatigue, somnolence or sleep disturbance (9%). Similar types of adverse events were also reported in sham conditions.
Serious adverse events were infrequently reported, with no consistent reports of seizures, persistent neurological deficits or treatment discontinuation. These findings are descriptive only. Adverse event monitoring methods were not described in 62% of studies, and the reported percentages represent the proportion of studies reporting each adverse event rather than participant-level incidence.
Therefore, the frequency of adverse events cannot be reliably estimated. Safety analyses exclude the 10 RCT protocols.
Discussion
We identified three key findings: (1) a predominant focus on M1 and DLPFC, reflecting a region-centric paradigm; (2) substantial heterogeneity in stimulation dosage and treatment schedules, with limited justification for parameter selection; and (3) inconsistent and poorly described safety monitoring, despite generally mild and transient adverse events.
The predominance of M1 and DLPFC as stimulation targets reflects their established roles in pain modulation and cognitive-affective processing, as well as their accessibility for stimulation using standard localisation methods.561244 High-frequency rTMS or anodal tDCS over M1 is thought to engage descending inhibitory pathways and modulate thalamocortical and corticospinal circuits implicated in pain perception.45 Its frequent use in osteoarthritis, chronic low back pain and fibromyalgia aligns with evidence of altered motor cortex excitability and impaired inhibitory control in these conditions. Similarly, the relatively high proportion of DLPFC targeting, particularly in fibromyalgia, is congruent with the role of this region in executive control, emotion regulation and top-down modulation of pain-related salience and affect.46 However, despite this theoretical grounding, the overwhelming reliance on a limited number of canonical targets suggests that most studies used conventional region-based targeting, with limited explicit implementation of network-informed targeting approaches. Exploratory targeting of other regions (eg, S1, operculo-insular cortex, associative or deep cortical targets) was rare and typically limited to single studies.
This imbalance indicates that the explicit translation of emerging network-based pain models into experimental NIBS designs remains limited.47
Although commonly accepted within-session dosage parameter ranges are evident, such as 10 Hz rTMS at 80–120% rest motor threshold and tDCS at 1–2 mA for 20–30 min, substantial variability exists in treatment schedules and cumulative exposure. Importantly, fewer than half of the studies justified frequency or intensity selection, and treatment duration was least frequently justified. This pattern suggests that most protocols are inherited from prior trials or safety guidelines rather than derived from systematic dosage-response investigations or individualised neurophysiological considerations.
This reliance on empiricism may partially explain inconsistent clinical outcomes reported in the broader NIBS literature; however, because this review did not evaluate whether dosage-selection strategies were associated with effectiveness, this interpretation remains a hypothesis to be tested in future research. Chronic pain is characterised by marked inter-individual variability in cortical excitability, lateralisation, network connectivity and psychosocial contexts, all of which may influence responsiveness to stimulation.48–50 Uniform dosage paradigms may therefore obscure meaningful treatment effects in responsive subgroups. Incorporating adaptive dosage strategies, baseline neurophysiological stratification and mechanistic biomarkers could facilitate a shift toward precision neuromodulation; these approaches are proposed as directions for future research rather than conclusions of the present review.51 Furthermore, clearer reporting of cumulative dosage and maintenance or booster strategies is essential to enable replication and secondary analyses.5253
Some studies combined NIBS with exercise therapy, education or other rehabilitation interventions, particularly in tDCS trials. Such combinations are consistent with the proposed role of neuromodulation as an adjunct to behavioural or physiotherapy interventions.54 However, the present review did not evaluate the incremental or synergistic effects of combined interventions. Future studies should therefore clarify the intended role of NIBS as a standalone analgesic vs adjunctive intervention and investigate how concomitant therapies influence dosage requirements and treatment outcomes.
Across modalities, reported adverse events were predominantly mild, transient and similar between active and sham conditions. Headache, local discomfort and cutaneous sensations were most common, consistent with previous neuromodulation literature.25 However, these findings should be interpreted cautiously because the quality and consistency of safety monitoring and reporting were limited. Nearly two-thirds of included studies did not clearly describe how adverse events were assessed, and only a small minority employed structured instruments, severity grading or standardised definitions.
This lack of methodological transparency limits confidence in safety conclusions and impedes synthesis across studies. Given that NIBS directly modulates brain activity and that rare but serious adverse events have been reported in other contexts,55 adoption of standardised adverse event reporting frameworks, such as structured checklists with severity and relatedness ratings, should be considered a minimum requirement for future trials.
Several limitations should be acknowledged. First, this scoping review did not assess methodological quality or risk of bias and therefore cannot make inferences regarding the efficacy or comparative effectiveness of NIBS interventions. Second, substantial heterogeneity in study designs, participant populations, stimulation protocols, outcome measures and reporting practices precluded quantitative synthesis and limited direct comparisons across studies.
Given that our objective was to map reporting practices across the full spectrum of CMP rather than to compare broad condition subgroups, we summarised studies descriptively by condition, presenting fibromyalgia, the largest subgroup, separately. Formal stratification and statistical comparison by fibromyalgia vs non-fibromyalgia CMP fell outside the descriptive scope of this review, though such comparisons represent a valuable direction for future work. Furthermore, incomplete reporting of key methodological details, particularly the rationale for stimulation dosage and approaches to safety monitoring, may have obscured the extent of variability in NIBS protocols and safety practices.
Third, the restriction to English-language publications may have resulted in the omission of relevant evidence published in other languages, potentially introducing language bias and limiting the generalisability of the findings beyond English-speaking contexts. Finally, trial registries and grey literature sources were not searched, meaning that unpublished studies and ongoing or planned protocols may have been missed. This may have limited the completeness of the evidence map, particularly with respect to emerging NIBS protocols.
Despite these limitations, this review provides a comprehensive mapping of the current NIBS landscape in CMP and identifies critical gaps to inform future research and guideline development. Future NIBS studies should investigate whether network-informed targeting can improve the mechanistic specificity and clinical effects of NIBS in CMP, since evidence suggests that chronic pain involves distributed brain networks.656 The results may inform future systematic reviews, clinical trials and guideline development to optimise the use of brain stimulation techniques for the management of CMP. Ultimately, this review supports researchers and clinicians in developing more targeted and effective neurostimulation strategies for patients with CMP, underpinned by transparent and standardised safety monitoring.
Conclusion
The use of NIBS for CMP is supported by a growing but methodologically heterogeneous body of literature. While M1 and DLPFC are consistently targeted across rTMS, TBS and tDCS, and broadly accepted intensity ranges are commonly applied, substantial variability and incomplete reporting persist in dosage selection, outcome measurement and safety monitoring. Reported adverse events were predominantly mild and transient, but inconsistent reporting of adverse event ascertainment limits interpretation, and the safety profile of NIBS in CMP remains incompletely characterised.
Current practice is largely driven by precedent rather than by mechanism-based optimisation or dosage-response evidence. Advancing this field will require a shift toward theoretically grounded, network-informed and systematically optimised protocols, supported by transparent reporting standards.
Supplementary material