神经病理性疼痛在临床上缺乏有效的镇痛药，因而有待发现新的有效的治疗靶点。最新研究显示，感觉神经节内免疫分子Toll样受体(TLRs)能调节神经元兴奋性和感觉信息传递。因此，我们用Real-time PCR检测了L5脊神经结扎(SNL)后10天，小鼠背根神经节(DRG)内所有功能性的TLRs(TLR1-9,11-13)基因表达，结果显示TLR8表达增加倍数最高。然而，TLR8在神经病理性疼痛中的作用和机制未见任何报道。为此，本项目将采用SNL诱导的神经病理性疼痛模型和行为学、形态学、分子生物学、药理学、电生理学等方法，研究(1)SNL后DRG中TLR8表达的时程、细胞定位和细胞器定位；(2)DRG中TLR8在神经病理性疼痛发生和维持中的作用；(3)TLR8参与疼痛调节的下游信号通路。本研究不但系统地阐明感觉神经节中TLR8调节神经病理性疼痛的机制，也为研发以TLR8为靶点的镇痛药物提供思路。

Neuropathic pain is lacking of effective analgesics in clinic. The development of new and effective targets is urgently needed. Recent researches showed that immune molecular TLRs (Toll-like receptors) are expressed in peripheral sensory ganglion and regulate neuronal excitability and transmission of sensory information. By using Real-time PCR, we investigated the expression of all functional TLRs (TLR1-9, 11-13) in the dorsal root ganglion (DRG) in mice after L5 spinal nerve ligation (SNL). The results showed the TLR8 mRNA was the most increased TLR. However, the role of TLR8 in neuropathic pain is unknown. Using SNL-induced neuropathic pain model, combining, behavior test, morphological, molecular biological, pharmacological and electrophysiological methods, we will investigate: (1) The expression and cellular and organelle distribution of TLR8 in DRG after SNL; (2) The role of TLR8 in DRG in the development and maintenance of neuropathic pain; (3) The downstream signal pathway of TLR8 underlying neuropathic pain. This project will not only unveil the mechanism of TLR8 in mediating neuropathic pain, but also provide evidence for the development of the novel analgesics by targeting on TLR8.