胶质细胞TSPO抗神经病理性疼痛的机制研究

脊髓背角胶质细胞通过分泌致炎细胞因子在神经病理性疼痛的维持中起关键作用。我们最近研究发现，腰5脊神经结扎（L5 SNL）引起脊髓背角星形、小胶质细胞TSPO表达上调，同时L5 SNL后7d 鞘内注射TSPO激动剂可抑制触诱发痛。体外实验研究发现，TSPO激动剂抑制培养的星形胶质细胞释放TNF-α，提示TSPO可能有抑制神经病理性疼痛发展的作用，并与胶质细胞活动有关，但其确切的作用机制尚不清楚。本项目拟用分子生物学，电生理等多种方法，观察TSPO激动剂、基因沉默对脊髓背角胶质细胞致炎细胞因子表达、释放的影响并进一步探讨MAPK、NF-kB通路在其中的作用，同时研究胶质细胞TSPO是否通过抑制致炎细胞因子的表达而影响背角神经元信息传递的效能，以期阐明TSPO抗神经病理性疼痛的作用机制，为研发新型镇痛药物提供实验证据。

Proinflammatory cytokines released from glial cells in the spinal dorsal horn play an important role in the maintenance of neuropathic pain. Our recent studies showed that the immunoreactivity (IR) of TSPO was increased in astrocytes and microglia in the L5 spinal dorsal horn following L5 spinal nerve ligation (L5 SNL) and that intrathecal injection of a specific TSPO agonist 7 days after L5 SNL could reverse the established mechanical allodynia. In vitro, TSPO agonist substantially attenuated TNFα release from cultured astrocytes. These results suggest that TSPO could reverse neuropathic pain, which is related to glia cells, but the exact mechanism is still unclear. In the present study, we will examine whether TSPO agonist and SiRNA influence the expression and release of proinflammatory cytokines in glia cells, and examine whether MAPK,NF-kB is involved in this process. Meanwhile we will examine whether TSPO in glia cells affect the excitatory transmission to Substantia Gelatinosa (SG） neurons in the spinal dorsal horn. Thus we will elucidate the mechanisms that TSPO inhibit neuropathic pain, and serve to develop new analgesics.