A型肉毒毒素调控脊髓胶质细胞治疗神经病理性疼痛的作用及其机制

A型肉毒毒素（BoNT/A）局部注射对临床多种病理性疼痛疗效显著，但其中枢作用机制尚不明确。我们前期研究表明，外周神经损伤后表达上调的脊髓胶质细胞、肿瘤坏死因子-α(TNF-α)及电压门控钠通道对神经病理性疼痛的产生和维持有重要意义。通过预实验我们发现，一侧足底注射BoNT/A可迅速减轻腰5前根切断（L5VRT）引起的双侧病理性疼痛症状，且可抑制脊髓胶质细胞的激活和TNF-α的过表达。因此我们设想，BoNT/A可能在中枢神经系统通过调控脊髓胶质细胞激活及TNF-α的释放，发挥镇痛作用。本项目拟在L5VRT疼痛动物模型确认BoNT/A逆行转运至中枢神经系统的作用，研究BoNT/A对脊髓胶质细胞激活及其释放TNF-α的调控机制，并进一步观察BoNT/A对背根神经节中钠通道表达和功能的影响，旨在揭示BoNT/A治疗神经病理性疼痛的中枢机制，为进一步应用BoNT/A治疗各种疼痛提供重要的理论依据。

Botulinum toxin type A (BoNT/A) has been used to treat a number of pain conditions including neuropathic pain, but its internal mechanism remains largely unknown. Our previous studies showed that the over expression of glial cells, tumor necrosis factor-ahpha(TNF-α) and voltage gated sodium channels following nerve injury contribute to the mechanism of neuropathic pain. Our preliminary experiments have indicated that subplantar injection of BoNT/A in the ipsilateral hindpaw reversed Lumbar 5 ventral root transection (L5VRT) induced neuropathic pain bilaterally. We assume that BoNT/A may exert its analgesic effect by regulating the activation of glial cells and the expression of TNF-α in CNS. The present study propose to examine the existence of axonal transport of peripherally applied BoNT/A to spinal cord; The mechanism of activation of glial cells and exression of TNF-α regulated by BoNT/A is studied in L5VRT animals. Furthermore, the effect of BoNT/A on the expression and function of sodium channels in dorsal root ganglions is also investigated. The research is expected to reveal the central mechanism of BoNT/A on neuropathic pain, thus provide important theoretical basis for the further application of BoNT/A on treatment of various pain.