The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury

The purpose of this study was to determine whether the timing of tread-mill exercise application can control expression levels of neuropathic pain- and regeneration-related proteins in the ipsilateral lumbar 4 (L4) to 6 (L6) dorsal root ganglion cells (DRG) after sciatic nerve injury (SNI). The experimental rats were randomly divided into five groups: the normal control, SNI+sedentary (IS), exercise+SNI (EI), SNI+exercise (IE), exercise+SNI+exercise (EIE) groups. The rats in exercise groups per-formed treadmill exercise at a speed of 8 m/min for 30 min once a day during 14 days before and/or after SNI. For investigating the expression of specific neuropathic pain and regeneration-related proteins in DRG, we prepared L4 to L6 DRG in the ipsilateral side. In the quantitative analysis, growth associated protein 43 (GAP-43) and brain-derived neurotrophic factor levels were further increased in the ipsilateral DRG at all treadmill exercise groups than those in IS group. In the histological findings, GAP-43 was qualitatively increased IE and EIE groups than IS group at DRG. Wnt3a and β-catenin were dramatically downregulated in EIE and IE groups than IS groups. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-α were significantly decreased in IE and EIE groups than IS group in the ipsilateral DRG. Our findings suggested novel information that regular low-intensity exercise before and/or after SNI might be a therapeutic and preventive approaches for relieving neuropathic pain and improving axonal elongation after peripheral nerve injury.