One of the potential mechanisms of motor cortex stimulation by noninvasive brain stimulation (NIBS) effects on pain is through the restoration of the defective endogenous inhibitory pain pathways. However, there are still limited data on quantitative sensory testing (QST), including conditioned pain modulation (CPM), supporting this mechanism. This systematic review and meta-analysis aimed to evaluate the effects of noninvasive motor cortex stimulation on pain perception as indexed by changes in QST outcomes. Database searches were conducted until July 2019 to include randomized controlled trials that performed sham-controlled NIBS on the motor cortex in either the healthy and/or pain population and assessed the QST and CPM. Quality of studies was assessed through the Cochrane tool. We calculated the Hedge's effect sizes of QST and CPM outcomes and their 95% confidence intervals (95% CIs) and performed random-effects meta-analyses. Thirty-eight studies were included (1178 participants). We found significant increases of pain threshold in healthy subjects (ES = 0.16, 95% CI = 0.02-0.31, I2 = 22.2%) and pain populations (ES = 0.48, 95% CI = 0.15-0.80, I2 = 68.8%), and homogeneous higher CPM effect (pain ratings reduction) in healthy subjects (ES = −0.39, 95% CI = −0.64 to −0.14, I2 = 17%) and pain populations (ES = −0.35, 95% CI = −0.60 to −0.11, I2 = 0%) in the active NIBS group compared with sham. These results support the idea of top-down modulation of endogenous pain pathways by motor cortex stimulation as one of the main mechanisms of pain reduction assessed by QST, which could be a useful predictive and prognostic biomarker for chronic pain personalized treatment with NIBS.

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique which has been widely studied for the treatment of chronic pain. It is considered a promising and safe alternative pain therapy. Different targets have been tested, each having their own particular mechanisms for modulating pain perception. Areas covered:We discuss the current state of the art of tDCS to manage pain and future strategies to optimize tDCS' effects. Current strategies include primary motor cortex tDCS, prefrontal tDCS and tDCS combined with behavioral interventions while future strategies, on the other hand, include high intensity tDCS, transcutaneous Spinal Direct Current Stimulation, cerebellar tDCS, home-based tDCS and tDCS with extended number of sessions.Expert commentary: It has been shown that the stimulation of the prefrontal and primary motor cortex is efficient for pain reduction while a few other new strategies, such as high intensity tDCS and network-based tDCS, are believed to induce strong neuroplastic effects, although the underlying neural mechanisms still need to be fully uncovered. Hence, conventional tDCS approaches demonstrated promising effects to manage pain and new strategies are under development to enhance tDCS effects and make this approach more easily available by using, for instance, home-based devices.

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