Regular Swimming Exercise Attenuated Neuroma Pain: Involvement Of Leptin And Adiponectin

Objectives: Accumulating evidence demonstrates the beneficial effects of physical exercise on pain conditions,however,the underlying mechanisms have not been thoroughly understood.The purpose of the present study was to investigate the effects of regular swimming exercise on neuroma pain and the possible roles of adipokines(leptin and adiponectin)in the pain behaviors modulated by exercise.Methods: The tibial neuroma transposition(TNT)was adopted to establish animal model of neuroma pain,animals were subjected to regular swimming exercise after seven days' recovery from surgery.Behavioral tests were carried out at different time points to evaluate the changes of pain behaviors.Moreover,biochemical or immunohistochemical tests were performed to evaluate the plasma levels of leptin and adiponectin,the expressions of leptin receptor and adiponectin receptors in neuroma,and the morphology of tibial nerve or neuroma.Finally,exogenous leptin or exogenous adiponectin was injected into the neuroma site to further investigate their roles in the pain behaviors.Results: The results showed that five weeks of regular swimming exercise alleviated both long-lasting neuroma tenderness at the lateral side of ankle and allodynia at the hind paw plantar induced by TNT surgery.Also,regular swimming exercise suppressed the formation of neuroma and promoted the morphological recovery of injured nerve.Moreover,TNT surgery increased leptin level in plasma and upregulated expression of its receptor Ob-Rb in neuroma,decreased adiponectin level in plasma and downregulated expression of its receptor AdipoR1 in neuroma;whereas regular swimming exercise normalized the dysregulation of circulating leptin and adiponectin in plasma induced by TNT surgery,and reversed the altered expressions of leptin receptor Ob-Rb and adiponectin receptor 1 in neuroma induced by TNT surgery.The time points of these changes were in accordance with that of behavioral changes.In addition,local administration of exogenous leptin to the neuroma site dampened the analgesic effects of regular swimming exercise on neuroma tenderness and local administration of exogenous adiponectin to the neuroma site alleviated the neuroma tenderness in the non-exercised neuroma rats.Conclusion: The current study demonstrates that five weeks of regular swimming exercise relieved pain behaviors in a rat model of neuroma pain and suggests that leptin and adiponectin might be involved in mediating the beneficial effects of regular swimming exercise on neuroma pain,thus presents them as potential targets for pain management.