5China Institute of Sport and Health Science, Beijing Sport University, Beijing, China4College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an, China3Junqi Wu is the co-first author1Department of Exercise Physiology, Beijing Sport University, Beijing, China2School of Education, Xiamen Nanyang University, Fujian, China
BACKGROUND The prefrontal cortex is a key brain region involved in pain-related processing. Exercise has been recognized as an effective non-pharmacological intervention for alleviating neuropathic pain; however, whether exercise exerts analgesic effects through modulation of the PFC and the underlying mechanisms remain unclear. This study aimed to investigate the role of the PFC in exercise-induced analgesia and to explore the potential involvement of TGF-β1 signaling and astrocyte activity. M...更多
BACKGROUND The prefrontal cortex is a key brain region involved in pain-related processing. Exercise has been recognized as an effective non-pharmacological intervention for alleviating neuropathic pain; however, whether exercise exerts analgesic effects through modulation of the PFC and the underlying mechanisms remain unclear. This study aimed to investigate the role of the PFC in exercise-induced analgesia and to explore the potential involvement of TGF-β1 signaling and astrocyte activity. METHODS A spared nerve injury –induced neuropathic pain model was established in C57BL/6 J mice. Mice in the exercise group underwent low-intensity aerobic treadmill training . Mechanical and cold pain behaviors were assessed, and molecular and histological analyses of the PFC were performed. RESULTS SNI led to foot after mechanical and cold pain hypersensitivity in mice , reduce the expression of transforming growth factor - beta 1 , increased astrocyte activation as indicated by elevated GFAP immunoreactivity , and decreased the co-localization of TGF-β1 with astrocytes . In SNI mice, exercise significantly attenuated pain hypersensitivity , reduced astrocyte activation , restored TGF-β1 expression , and increased TGF-β1–astrocyte co-localization in the PFC . Intrathecal administration of TGF-βR type Ⅰ receptor inhibitor attenuated exercise analgesia , enhanced astrocyte activation , and decreased TGF-β1 expression . CONCLUSIONS These findings suggest that aerobic exercise is associated with the restoration of TGF-β1/TGF-βRI signaling and attenuation of astrocyte activation in the PFC following peripheral nerve injury, which may contribute to exercise-induced analgesia. This study provides mechanistic insight into the role of PFC astrocytes and TGF-β1 signaling in the beneficial effects of exercise on neuropathic pain.收起
