Abstract
We aimed to minimize the frequency of exercise intervention and test the efficacy of pain relief. We also investigated the mechanism of neuropathic pain to determine the best frequency of pain relief for neuropathic pain. The chronic constriction injury (CCI) rat model was randomly divided into three groups: exercise (Ex), No-Ex, and normal. The treadmill exercise intervention was administered, and the 50% withdrawal threshold was assessed using the Von Frey Test. Ionized calcium-binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), C-C chemokine receptor type 2 (CCR2), and tumor necrosis factor receptor-associated factor 6 (TRAF6) activation was determined through immunohistochemistry. In the brain, we examined the increased expression of β-endorphin/met-enkephalin in the gray matter of the midbrain aqueduct. Co-expression of CCR2, IBA1, and Neu-N was observed in the spinal cord dorsal horn by immunofluorescence staining. The 50% pain response threshold was significantly lower in the Ex group than in the No-Ex group at five weeks post-CCI, indicating a high analgesic effect. In the dorsal horn of the spinal cord, IBA1 and GFAP were significantly decreased in the Ex group than in the No-Ex group at five weeks post-CCI. However, no significant difference in activation of BDNF, CCR2, and TRAF6 was observed. In the midbrain, the Ex group showed a significant increase compared to the No-Ex group. In summary, our results suggest that in minimal-exercise intervention, neuropathic pain relief is achieved by activation of the descending pain inhibitory system in the midbrain.