类风湿关节炎（RA）关节疼痛是以痛阈降低、痛觉敏感为主要特征，严重影响人民身心健康的慢性神经性疼痛。研究显示，在RA关节增生组织中大量肥大细胞积聚并活化，是促进关节疼痛持续发生发展的重要原因，因此通过抑制肥大细胞活化，可达到有效防治RA关节疼痛的目的。我们在前期实验中发现，资木瓜总苷通过抑制肥大细胞活化，降低组胺（Histamine）的表达水平，减轻关节痛觉敏感，对实验性RA关节疼痛起治疗作用。本项目拟在此基础上，进一步利用抗体诱导性小鼠单关节炎模型，建立肥大细胞-DRG细胞（关节背根神经节细胞）共培养体系，通过体内外的实验，探讨资木瓜总苷经肥大细胞-Histamine -H-1-TRPA1-DRG信号分子网络系统的途径抑制肥大细胞活化，促进DRG细胞凋亡，降低痛觉感受器敏化作用分子机理，阐明资木瓜总苷抗RA关节疼痛作用机制，为以肥大细胞为靶点的新型RA镇痛药物研究提供理论和实验依据

Rheumatoid arthritis (RA) joint pain, which is characterized by reduced pain threshold and pain sensitive, is chronic immune neuropathic pain influencing people's physical and mental health.Research showed that a large number of mast cells in RA joint hyperplasia tissue accumulation and activation, and was the important reason to promote the development of RA joint pain continuity, so by inhibiting the joint hyperplasia tissue mast cell activation, was expected to reach the purpose of effective prevention and treatment of RA joint pain. In previous experiments, we found that he total saponins extracted from chaenomeles speciosa (TSCS) could inhibit mast cell activation, reduce the expression level of histamine, thus reduce joint pain sensitivity, produce therapeutic effect on experimental RA joint pain. Based on these findings, in this project, we will further use of antibody induced monoarthritis model in mice, and mast cells-DRG cells (joint dorsal root ganglion cells) co-culture system to explore the functions of TSCS in inhibiting mast cell’s activation and thus promoting the DRG cells apoptosis, reducing pain receptors sensitization via mast cells-Histamine-H-1-TRPA1-DRG signaling molecules network system pathway in vivo and in vitro, and to illustrate the underlying molecular mechanism of TSCS in anti-RA joint pain . The successful implementation of this project will provide theoretical and experimental basis for development of new analgesic drug in RA that target in the mast cells.