Effect of treadmill exercise on pain-related Wnt/β-catenin signaling pathway in dorsal root ganglion neurons at the early phase regeneration of the injured sciatic nerve

The purpose of this study was to determine whether treadmill walking exercise can improve mechanical allodynia through regulation of Wnt/β-catenin signaling in dorsal root ganglion (DRG) neurons at the early stage of regeneration after sciatic nerve injury (SNI). The experimental rats were divided into seven groups: the normal control, sedentary groups for 3-, 7-, and 14-day post crush (dpc), and exercise group for 3, 7, and 14 dpc. The rats in exercise groups performed treadmill walking exercise at a speed of 8 m/min for 20 min once a day according to experiment duration. For evaluating neuropathic pain-like behavior after SNI, the mechanical allodynia was examined by von Frey apparatus. And the expression levels of pain-related protein were identified in the cytoplasm or nucleus of DRG neurons using Western blot techniques. Mechanical allodynia was significantly ameliorated in the exercise group at 7 and 14 dpc. Treadmill exercise further decreased Wnt3a expression at 3, 7, and 14 dpc compared to in the sedentary group. Also, phosphorylated-low-density lipoprotein receptor 6 was decreased in exercise groups at 3 and 14 dpc. Beta-catenin was significantly decreased in exercise groups at 3 and 14 dpc compared to sedentary groups as well as treadmill exercise decreased translocation of β-catenin towards the nucleus of DRG neurons at 14 dpc. Our findings indicate that treadmill walking exercise may be an important regulator of neuropathic pain after peripheral nerve injury through delayed Wnt/β-catenin signaling pathway in DRG neurons.