三叉神经痛是由于三叉神经根受脑血管压迫发生脱髓鞘变性而产生异位冲动，但其具体机制仍不详。我们前期研究发现：三叉神经痛患者血清中IL-6的水平明显高于健康志愿者，模型动物三叉神经节中有Nav1.3上调，且与IL-6、YAP等蛋白表达相关。由此推测：一定程度的脱髓鞘变性，可引起IL-6表达增多，后者激活YAP信号通路促进Nav1.3在三叉神经节的表达；因Nav1.3具有快速失活及复活的电生理特性，很易达阈值而开放，从而产生可传导的异位动作电位。本项目将应用RNA干扰、膜片钳、Luciferase报告基因系统、染色质免疫共沉淀等技术，探究导致Nav1.3高表达并发挥作用的信号通路，为临床将来研发能有效阻断该路径的新药提供理论依据。

Trigeminal neuralgia is a common disorder of cranial nerve hyperexcitability affecting living quality of the patient awfully, especially among the Orientals. Although the microvascular decompression surgery with elimination of the etiology (vascular compression) has resulted in a high postoperative cure rate, it is invasive with risk. Therefore, an alternative remedy without craniectomy is expected, which relies on deeper understanding of its pathogenesis. Regardless demyelination has been exhibited as the pathological precondition igniting ectopic impulses from the fifth cranial nerve fibers, the detailed mechanism has been still unclear so far. ..Our pilot studies have observed the serum levels of IL-6 in TN patients were significantly higher than that in healthy volunteers. Moreover, we found the up-regulation of Nav1.3 in the trigeminal neuralgia model animal, which were correlated with the expression of those proteins, such as IL-6, YAP and so on...Accordingly, we propose a hypothesis as followings:.A certain degree of demyelination of the nerve may give rise to an increase in inflammatory cytokines including IL-6, which activate the Hippo/YAP signaling pathway and then promote expression of Nav1.3. Because Nav1.3 mediates a current with fast activation and inactivation kinetics, it is susceptible to reach its threshold and a conductible ectopic action potential is eventually generated from the trigeminal nerve. ..To prove the role Nav1.3 in generation of ectopic action potential from the fifth cranial nerve, we will carry out a series of experiments with emphasis on the signal pathway using molecular biology and electrophysiology techniques such as siRNA interference, Luciferase report gene system, Chromatin immunoprecipitation and patch clamp. Hopefully, the results from this investigation could serve as a theoretical foundation for the feasibility to develop a noninvasively targeted remedy for trigeminal neuralgia in the future clinical practice.