初级感觉神经元内Nogo-A调控痛觉敏化过程中TRPV1通道功能的研究

背根神经节(DRG)内TRPV1通道是炎症痛等病理性痛觉敏化的关键分子，而其激动剂或拮抗剂作为镇痛药物具有明显的副作用，目前针对TRPV1的调控机制的研究成为镇痛药开发的重要方向。我们前期研究发现，特异性表达于DRG神经元中Nogo-A 蛋白在炎症痛的初期即迅速增加，干预Nogo-A的功能可快速降低炎症刺激所致DRG中TRPV1含量的升高，消弱TRPV1功能，缓解热痛觉敏化。据此，提出"DRG中的Nogo-A通过调控TRPV1生物学特性及功能参与炎症痛觉敏化"的科学假说。围绕该假说，本项目拟采用多种研究手段，在分子、细胞和整体动物水平，首先确定DRG 神经元内的Nogo-A 蛋白参与了痛觉敏化，继而探讨其通过影响TRPV1的表达或功能参与痛敏过程，试图在揭示Nogo-A 蛋白新功能的同时，探讨其对TRPV1的调控作用，为设计开发特异性的镇痛药提供新的思路，具有重要的理论意义和实际应用前景。

The TRPV1 channel in DRG is the key molecule for development of the heat hyperalgesia ,which results from tissue inflammation or physical injury. However, its blocker or antagonist have obvious side effects as the analgesics. Nowadays the study of the modulation of TRPV1 channel is becoming a new field to exploit the noval analgesics. Our previous study showed that Nogo-A protein which is specifically expressed in DRG neurons dramatically encreased at the beginning stage of the inflammation pain.Interfering the function of Nogo-A significantly reduce the amount and function of the TRPV1.So we proposed the hypothesis that Nogo-A in DRG neurons participates in the inflammatory hyperalgesia through modulating the biological characteristics or function of TRPV1. This project will use multiple experimental methods on the base of fully pre-experiment and aims to first determine whether the Nogo-A protein in the DRG neurons is involved in the inflammatory hyperalgesia; then explore that whether Nogo-A is involved in hyperalgesia through modulation of biological characteristics and functions of TRPV1. This project attempt to reveal a new function of Nogo-A protein, and at the same time investigate its effects on TRPV1 regulation. Accomplishment of this project will provide a new idea for the development of new analgesic drugs with less side effect.?