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。我们的早期研究证实骨性关节炎（OA）所致的慢性持续性疼痛是一种慢性神经病理性疼痛，而非单纯炎症性疼痛。如何有效逆转该疼痛，以期改进临床药物治疗成为一个亟待解决的问题。我们的预实验揭示：在OA疼痛模型中CACNA2D1表达明显上调，而使用CACNA2D1靶向抑制剂后此种上调被逆转。提示：CACNA2D1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"CACNA2D1-CGRP通路参与调制骨性关节炎痛觉过敏的效应"的观点，推测CACNA2D1-CGRP途径可能与OA痛发生及进展密切相关。研究采用基因过表达、RNAi等技术，从细胞、组织和动物实验三个水平检测CACNA2D1-CGRP通路在介导OA痛的发生进展中的作用，从而为寻找OA疼痛治疗的新途径、新方法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. 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 CACNA2D1 expression were greatly up-regulated in the OA model, while this trend was reversed with CACNA2D1 targeted-inhibitor. It suggests that CACNA2D1 may mediate the occurrence and progression of OA-induced pain. Based on our prior results and latest literature, we speculated that "CACNA2D1-CGRP pathway is involved in modulating OA-induced hyperalgesia" and CACNA2D1-CGRP pathway may be closely related to the occurrence and progression of OA-induced pain. In this study, gene over-expression, RNA interfer and molecular biology techniques etc will be used to tesitify the function and molecular mechanism of CACNA2D1-CGRP 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.