神经病理性疼痛是困扰临床的重要难题，机制不清。内吞蛋白Endophilin A2广泛分布于神经系统，调控多种功能，但其在病理性疼痛中的作用还未有研究。前期预实验显示：1)神经损伤上调大鼠背根神经节（DRG）Endophilin A2的表达，且促进其与Nav1.7结合；2)鞘内给予Endophilin A2中和性抗体，不仅能降低神经损伤诱导的DRG神经元兴奋性增强，缓解神经病理性疼痛，还抑制Nav1.7膜转位；3)Endophilin A2与驱动蛋白KIF5B相结合。据此我们推测：Endophilin A2可能通过与Nav1.7和KIF5B形成复合体，在KIF5B的驱动下，调控Nav1.7膜转位，介导神经病理性疼痛。本项目拟采用膜片钳和多种分子生物学技术，明确Endophilin A2在神经病理性疼痛中的作用，并深入探讨其调控Nav1.7膜转位的分子机制，为防治神经病理性疼痛提供新的靶点。

Neuropathic pain is an important clinical problem, and the mechanism is not clear. Endophilin A2 is widely distributed in the nervous system and regulates many functions, while the role of Endophilin A2 in neuropathic pain is not clear. Our previous findings suggested that: 1) nerve injury significantly increased the abundance of Endophilin A2 and promoted the interaction with Nav1.7 in the dorsal root ganglion (DRG) tissues; 2) neutralized Endophilin A2 significantly inhibited the hyperexcitability of DRG neurons, neuropathic pain and trafficking of Nav1.7; 3) Endophilin A2 interacts with KIF5B in SNI rats’ DRG tissues. So we hypothesized that the increased Endophilin A2 interacts with KIF5B and Nav1.7 to form a complex, which promote the trafficking of Nav1.7 and contribute to neuropathic pain. In this project, the patch clamp and a variety of molecular biology techniques will be used to identify the functional role of Endophilin A2 in neuropathic pain and explore the mechanism of Nav1.7 trafficking. Our study will provide novel molecular target for prevention and therapy of neuropathic pain.