BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference 2.06, 95% confidence interval 1.35 to 2.78, I2 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.

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