CD40/CD40L调控NF-κB信号通路在骨性关节炎慢性疼痛中作用及机制

不能有效缓解骨性关节炎（OA）所致的慢性持续性疼痛是临床药物治疗失败的重要原因之一。在国家自然科学基金青年项目资助下，我们的研究证实OA所致的慢性持续性疼痛是一种信号转导通路参与的慢性神经病理性疼痛。我们最近的预实验揭示：在炎症模型中CD40可有效调控NF-κB信号转导通路。提示：CD40/CD40L很可能介导OA痛的发生及进展。本项目基于既往研究结果和文献分析，提出“CD40/CD40L调控NF-κB信号通路参与骨性关节炎慢性疼痛”的观点，推测CD40/CD40L调控NF-κB信号通路途径可能与OA痛发生及进展密切相关。研究采用siRNA、Western blot、免疫荧光、胶体金免疫电镜、激光共聚焦等技术，从细胞、组织和动物实验三个水平检测CD40/CD40L调控NF-κB信号通路在介导OA痛的发生进展中的作用，从而为寻找OA疼痛治疗的新方案以及为寻找新型药物靶点提供理论依据。

One of the important reasons for clinical drug treatment failure is not to relieve effectively osteoarthritis (OA)-induced chronic persistent pain. We found that OA-induced chronic persistent pain was a chronic neuropathic pain rather than a simple inflammatory pain, which is regulated by signal transduction pathway . How to effectively reverse this pain in order to improve clinical drug therapy becomes an urgent problem to be solved. Our preliminary experiments revealed that NF-κB signal pathway expression were greatly up-regulated by CD40. It suggests that CD40 may mediate the occurrence and progression of OA-induced pain. Based on our prior results and latest literature, we speculated that “CD40/CD40L-NF-κB signal pathway is involved in modulating OA-induced hyperalgesia” and may be closely related to the occurrence and progression of OA-induced pain. In this study, siRNA, immunofluorescence, immuno-electron microscope, HPLC-MS, laser confocal microscopy, western blot and other methods will be used to tesitify the function and molecular mechanism of CD40/CD40L-NF-κB pathway in OA-induced pain, as well as animal experiment, to provide a strong evidence and theoretical basis in clinical OA-induced chronic pain treatment and research.