Strength training attenuates neuropathic pain by Preventing dendritic Spine dysgenesis through Suppressing Rac1 and inflammation in experimental autoimmune encephalomyelitis

Chronic pain is a challenge and major health problem to basic science and clinical practice. Pain is one of the worst symptoms of multiple sclerosis (MS), which has a significant impact on their quality of life. Rac1 is an important intracellular signaling molecule involved in spinal dendritic spine pathology and activation of IL-1 beta and TNF-alpha that are associated with chronic neuropathic pain. As a result, targeting Rac1 presents a promising approach to managing neuropathic pain. Clinical studies have demonstrated that physical exercise is a non- pharmacological strategy that positively influences disease progression in individuals with MS, but underlying mechanism of exercise on Rac1- induced neuropathic pain is not well understood. This study examined the effects of a 4-week strength training on Rac1 expression, IL-1B, TNF-alpha, TGF-beta 1 levels, MDA concentrations, SOD activity, dendritic spine abnormalities in the dorsal horn of the spinal cord, as well as nociceptive behaviors (formalin test) and motor function (Rotarod test) during the chronic phase of experimental autoimmune encephalomyelitis (EAE). The findings indicated that strength training increased TGF-beta 1 expression and SOD activity while decreasing the expression of Rac1, IL-1 beta, TNF-alpha, and MDA and reducing dendritic spine dysgenesis in the dorsal horn of the spinal cord. We observed strength training effectively reduced nociceptive behaviors and improved motor function in mice with EAE. In summary, regular physical exercise may modulate neuropathic pain through inhibition of dendritic spine dysgenesis, inflammation and oxidative stress in the dorsal horn of the spinal cord.