Exercise-induced hypoalgesia: potential mechanisms in animal models of neuropathic pain.

Abstract

Physical exercise, such as forced treadmill running and swimming, can sufficiently improve mechanical allodynia and heat hyperalgesia in animal models of neuropathic pain (NPP), including partial sciatic nerve ligation, chronic constriction injury, and spinal nerve ligation models. Thus, physical exercise has been established as a low-cost, safe, and effective way to manage NPP conditions, but the exact mechanisms underlying such exercise-induced hypoalgesia (EIH) are not fully understood. A growing body of evidence has identified several factors that work at different levels of the nervous system as playing important roles in producing EIH in animal models of NPP. The objective of this review is to provide an overview of key players associated with EIH, and then to discuss our current understanding of the mechanisms underlying EIH. Relevant studies have demonstrated that physical exercise can dramatically alter the levels of inflammatory cytokines, neurotrophins, neurotransmitters, endogenous opioids, and histone acetylation at various sites in the nervous system, such as injured peripheral nerves, dorsal root ganglia, and spinal dorsal horn in animal models of NPP, thereby contributing to the production of EIH. These results suggest that EIH is produced through multiple cellular and molecular events in the pain pathway.