TRPV1不仅是公认的参与病理性疼痛外周敏化的关键分子，近年来证实中枢TRPV1也发挥重要的痛觉调制作用。以TRPV1为靶点的镇痛药物前景良好，但现有TRPV1激动剂或拮抗剂在镇痛同时伴一定副作用而影响其在临床的使用。从TRPV1调节蛋白入手设计TRPV1功能干扰药物，或将是镇痛药物研发的新途径。本室预实验结果揭示神经元高表达的钙结合蛋白DREAM可与TRPV1结合，并抑制TRPV1膜表达，可能是TRPV1的负性调控蛋白。本项目拟在原有工作基础上，综合利用生物化学、分子生物学、电生理学和动物行为学等方法，对DREAM与TRPV1的相互作用及其对TRPV1通道电流、失敏和膜表达的调控和机制进行深入研究。更重要的是，我们拟根据DREAM与TRPV1结合的主要位点构建穿膜肽，观察其是否可抑制TRPV1功能并发挥镇痛作用。该研究对深入认识TRPV1调控机制，开发新型镇痛药物具有重要意义。

It is generally accepted that TRPV1 is a key molecule involved in the development of peripheral sensitization during pathological pain states. As reported recently, TRPV1 also plays a critical role in pain modulation in the central nervous system. Analgesics targeting TRPV1 are promising. However, both TRPV1 agonists or antagnists have some side effects when they are used for pain relief. It might be a new strategy for the development of analgesics based on the regulatory proteins of TRPV1, which can interfere with the function of TRPV1. Our preliminary data indicate that DREAM (downstream regulatory element antagonist modulator), a Ca2+-binding protein highly expressed in neurons, associates with TRPV1 and inhibits the surface localization of TRPV1. These findings imply that DREAM might be a negative regulator of TRPV1. In the present project, we will investigate the interaction between DREAM and TRPV1, the regulatory role of DREAM in TRPV1 channel current, desensitization and surface expression and reveal the underlying mechanisms, using biological chemistry, molecular biological, electrophysiological and behavioral methods. More importantly, we will construct the transmembrane peptides according to the critical binding sites of DREAM and detect their effects on TRPV1 channel function and the possible analgesic effects. These findings are of great significance for our understanding of the regulatory mechanisms of TRPV1 and the development of analgesics.