抄録
Physical exercise such as running or swimming can improve neuropathic pain (NPP) through alterations of cells that constitute the spinal dorsal horn,brainstem and injured peripheral nerve, but the exact mechanisms under lying exercise–induced hypoalgesia (EIH) are not fully understood. Since effects of physical exercise are influ enced by many factors including intensity, duration, frequency and style (forced exercise vs voluntary exercise) of exercise, the most suitable condition of exercise to produce EIH have not yet been determined in detail. The purpose of this review article is to compare the effects of forced treadmill running (FTR) and voluntary wheel running (VWR) in producing EIH in order to propose optimum exercise conditions to induce EIH. In addition, we described several potential mechanisms under lying EIH. In the case of FTR, we have demonstrated that exercise conditions composed of 1) acclimation to FTR prior to surgery, 2) initiation of FTR at an early stage after surgery and 3) enforcement of FTR for 60 min ⁄day, 5 days ⁄ week at low– or intermediate–exercise intensity are most effective in producing EIH. We further demonstrated that VWR can not only sufficiently produce EIH, but also improve pain behaviors more efficiently than FTR does. Our study suggested that initiation of VWR without delay after surgery may be an important factor to develop EIH. On the other hand, despite growing evidence showing the importance of γ–aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) 65 and 67 in the regula tion of NPP, the relevance of both factors to EIH is totally unknown. Immunofluorescence analysis showed that VWR significantly prevents sciatic nerve injury–induced reductions in GAD65 production in the superficial dorsal horn, and suggested that maintained GAD65 production may consequently contribute to the retention of GABA in interneurons and neuropils of the dorsal horn. Based on these findings, we propose that EIH is achieved, at least in part, by maintaining GABAergic inhibition in the spinal dorsal horn, and that VWR may be a potentially most suitable exercise style for producing EIH.
