Mechanisms underlying exercise-induced pain modulation in people with multiple sclerosis - a scoping review

Multiple Sclerosis (MS) is a prevalent chronic neuroinflammatory disease, characterized by demyelination, inflammation and axonal degeneration. Up to 40% of people with MS (pwMS) experience central neuropathic pain (CNP). Despite numerous debilitating consequences, CNP is often underdiagnosed and undertreated, with limited pharmacological options available. However, exercise is a promising non-pharmacological intervention in the management of pain. This scoping review therefore aims to (a) outline the pathophysiological mechanisms of CNP in MS, (b) summarize the neurophysiological effects of exercise on pain in MS, and (c) identify the mechanistic approaches through which exercise could modulate pain.

PubMed, EMBASE, Web of Science, and SPORTDiscus were searched using terms related to MS, exercise, and pain modulation. We included primary quantitative studies as well as relevant secondary evidence, investigating effects or mechanisms of exercise on recurrent, subacute, or chronic pain in pwMS. In the primary studies, pain was assessed through self-reported or objective measures.

Thirty-six articles were included. Mechanistic findings suggest that neuroinflammation, structural and functional central nervous system changes, and alterations in neurotransmitters and hormones contribute to pain in pwMS. Exercise may modulate several of these mechanisms, including inflammatory markers, neurostructural and functional brain changes, and pathways involving endocannabinoid and tryptophan systems.

Exercise may exert beneficial effects on central mechanisms relevant to pain modulation in pwMS, including neuroinflammatory pathways, neuroplastic adaptations, and neurotransmitter regulation. However, existing evidence is limited, warranting further high-quality research to fully clarify mechanistic links and establish exercise as a targeted non-pharmacological treatment for CNP in pwMS.