• Andrew Flood, Rocco Cavaleri, We-Ju Chang, Jason Kutch, Constantino Toufexis, and Simon J Summers.
• Research Institute for Sport and Exercise, University of Canberra, Bruce, ACT, Australia.
• Pain Med. 2024 Oct 15.

BackgroundNon-invasive brain stimulation (NIBS) has been investigated increasingly as a means of treating pain. The effectiveness of NIBS in the treatment of pain has traditionally focused upon protocols targeting the primary motor cortex (M1). However, over time, the effectiveness of M1 NIBS has been attributed to effects on interconnected cortical and subcortical sites rather than M1 itself. While previous reviews have demonstrated the effectiveness of non-M1 NIBS in improving subjective reports of pain intensity, the neurophysiological mechanisms underlying these effects remain incompletely understood. As chronic pain is associated with pain hypersensitivity and impaired endogenous descending pain modulation, it is plausible that non-M1 NIBS promotes analgesic effects by influencing these processes.ObjectiveThe aim of this systematic review and meta-analysis was therefore to evaluate the effect of NIBS over non-M1 sites on quantitative sensory testing measures in clinical pain populations.MethodsA systematic search of electronic databases was conducted from inception to January 2024. Included articles (13trials, n = 565 participants) were appraised using PEDro and GRADE and a random effects model was used to meta-analyse outcomes where possible.ResultsA small number of studies found that NIBS applied to DLPFC may improve pain modulation in patients with fibromyalgia, and that stimulation of the posterior superior insula and prefrontal cortex could improve pain sensitivity in chronic neuropathic and osteoarthritic pain, respectively. However, findings varied between studies and there remains a paucity of primary research.ConclusionThis review indicates that current literature does not provide clear evidence that NIBS over non-M1 sites influences pain processing.© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.

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