From heterogeneity to precision: Mapping the future of rTMS for musculoskeletal pain
(2025) British Journal of Pain — Vol. 19, n° 6, p. 374-376 (2025)
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Liberati, Giulia 
- Abstract
- Chronic musculoskeletal (MSK) pain remains one of the most pervasive causes of disability worldwide, affecting millions of individuals and imposing a substantial burden on patients, healthcare systems, and society. 1 As conventional pharmacological and physical therapies provide only partial pain relief, non-invasive brain stimulation has emerged as a compelling frontier. 2 In this issue of the British Journal of Pain, Liang et al. present a timely and comprehensive systematic review and meta-analysis on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for MSK pain, and on the stimulation parameters that may modulate efficacy. Their work adds an important piece to the growing puzzle of how non-invasive brain stimulation might contribute to pain alleviation. The review synthesizes data from 22 studies (23 trial comparisons), comprising over 1150 patients, and provides evidence of a significant reduction in pain intensity following active rTMS compared to sham, alongside improvements in mood and quality of life. These findings are clinically meaningful. They reinforce the idea that rTMS, originally developed as a research tool to probe cortical excitability, 3 may offer tangible benefit for chronic pain patients-particularly those for whom existing treatments provide incomplete relief. 4 The analysis also points to concrete factors that can inform clinical and research design. The finding that higher frequencies, intensities, and session numbers are associated with larger effects supports a dose-response relationship in neuromodulation-already observed for other disorders 5-offering practical guidance for balancing induction and maintenance phases of treatment. The methodological approach is comprehensive, combining a broad database search with standardized mean differences and sensitivity analyses to ensure the stability of the findings. No review to date has integrated this breadth of evidence across MSK conditions, making this synthesis an invaluable reference point for both clinicians and researchers. As with any meta-analysis pooling broad and varied literature, interpretation requires nuance. The reported heterogeneity is substantial, reflecting wide variability in both patient populations and stimulation protocols. The included studies span fibromyalgia, chronic low back pain, shoulder pain, and myofascial pain. While all "musculoskeletal," these conditions differ markedly in pathophysiology and central representation. Similarly, cortical targets ranged from the primary motor cortex (M1) to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), with stimulation frequencies from 1 to 20 Hz and session numbers from 1 to 20. This diversity reflects a field still exploring where and how rTMS exerts its effects, but it also means that the pooled estimate should not be interpreted as a one-size-fits-all measure of efficacy. Methodological quality is another source of variability. Nine of 22 studies failed to adequately describe random sequence generation, and only 10 employed allocation concealment-fundamental safeguards against selection bias that should be standard in ran-domized trials. This represents a high risk of bias in nearly half of the included evidence base. Without proper randomization and allocation concealment, systematic differences between groups at baseline may be mistaken for treatment effects, and no analytical approach can fully compensate for flawed trial design. Additionally, blinding integrity remains a challenge in rTMS pain research, where expectancy effects are non-trivial and sham procedures vary considerably in their credibility. These factors may contribute to inflated estimates of effect and deserve careful attention in future trials. It should be noted that the authors also performed multiple subgroup analyses examining frequency , intensity, and session number independently. These parameters are often interdependent (for instance , higher frequencies are frequently paired with higher intensities), complicating causal interpretation.
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Citations
Liberati, G. (2025). From heterogeneity to precision: Mapping the future of rTMS for musculoskeletal pain. British Journal of Pain, 19(6), 374-376. https://doi.org/10.1177/20494637251391429 (Original work published 2025)