膝骨关节炎（KOA）是骨科常见退行性疾病，致残率高。其病理机制尚不明确，治疗方案长期存在争议。如何有效缓解疼痛是临床亟需解决的难题。我们前期研究初步揭示了TRPs通道介导KOA冷痛敏和机械痛敏的病理机制，以及“温经活血”中药外治对其存在干预。. 细胞焦亡是Caspase-1依赖性的细胞促炎死亡模式，其全程均有大量炎性因子释放。前期研究中我们发现“温经活血”中药外治除抑制KOA滑膜组织TRPs上调，对激活TRPs的炎性因子等前驱环节也有干预作用。我们预实验在KOA滑膜组织检测到巨噬细胞焦亡关键激活者：炎性小体的核心组分NLRP3、ASC、caspase-1，高度提示巨噬样滑膜细胞焦亡可激活TRPs介导的KOA痛敏，而温经活血中药外治对此环节存在影响。. 本课题拟应用神经生物学疼痛行为检测和分子生物学基因蛋白检测、细胞膜离子通道的电生理特性检测等成熟技术，验证这一科学假说。

Knee osteoarthritis is a common degenerative disease in orthopaedics which has high disability rate, It yet lacks specific treatment due to the unclear pathogenesis. How to relieve the pain is the most urgent problem needed to be solved. Our previous research preliminarily reveals the pathogenesis that how TRP ion channels mediate cold hyperalgesia and mechanical hyperalgesia of knee osteoarthritis, which can be intervened by external therapy like warming channels activating blood circulation.. The pyroptosis of macrophagocyte was a new caspase-1 dependent death pattern of cells, with release of inflammatory cytokine during its process. In previous studies, we find out that the therapy warming channels activating blood circulation external therapy not only inhibits the up-regulated expression of TRPs in synovial tissues of knee osteoarthritis to a certain degree, but also has a role on regulation of inflammatory cytokine which can activate the TRP ion channels. Through the pre-test, we have detected the markers of pyroptosis of macrophagocyte in synovial tissues of knee osteoarthritis, NLRP3, ASC, caspase-1 provides evidence supporting the hypothesis that the pyroptosis of macrophage-like synoviocytes maybe activate the hyperalgesia of knee osteoarthritis mediated by the activation of TRPs. And the therapy warming channels activating blood circulation may influence this part.. This project intends to unite mature technology like detection on pain-related behaviors of neurobiology, gene protein of molecular biology and electrophysiological property investigation of ion channels in cell membrane, will be applied to test the scientific hypothesis.