基于TRP离子通道深入研究通络散结凝胶外用治疗大鼠骨癌痛的中枢分子机制

Cancer pain, one of the most common symptoms associated with malignancy, has a substantial impact on patients' activities and overall quality of life. TRP channels (TRPV1, TRPV4, TRPA1) play an important role on cancer pain of central mechanisms.TLSJ gel has been used for cancer pain by external treatment based on Traditional Chinese Medicine theory. Previously we reported that TLSJ gel significantly inhibits bone cancer-induced thermal and mechanical sensitization for useful in managing cancer pain and that it may act by inhibiting osteoclastic activity, ICTP and BAP levels of serum and cytokines. The aim of this study was to further evaluate the effects of TLSJ gel and to explore central mechanisms of TLSJ gel on bone cancer pain in a rat model by assessing both mechanical and thermal sensitivity, the BMD and BMC by imaging analysis system, TRPV1,TRPA1and TRPV4 activities of DRG, IL-1β and IL-17 levels in spinal cord with ELISA, Western-blot and immunohistochmistry.

癌性疼痛是恶性肿瘤常见症状之一，严重影响患者的生活质量。有效控制癌性疼痛是癌症患者治疗的重要内容之一。TRP离子通道（TRPV1，TRPV4，TRPA1）在机体中枢神经系统中与痛觉的形成及传导密切相关。在中医理论的指导下，通络散结凝胶外用治疗癌痛经济、安全有效。初步研究表明通络散结凝胶外用治疗癌痛主要通过缓解局部疼痛、抑制局部骨组织破骨细胞的活性、降低外周血ICTP和BAP的水平及炎性细胞因子而实现。本课题组在此基础上，复制大鼠骨癌痛模型，采用四足动态承重测试系统、von frey测痛仪、热刺激测痛仪、Prodigy双能X线骨密度仪、免疫组化、ELISA等方法从疼痛行为学、影像学、骨密度、背根神经节TRPV1，TRPV4及TRPA1的表达、脊髓炎性介质IL-1β和IL-17基因的表达等不同层次深入研究通络散结凝胶外用治疗癌痛的中枢分子机制，为临床治疗癌痛提供科学依据。

癌性疼痛是恶性肿瘤常见症状之一，严重影响患者的生活质量。有效控制癌性疼痛是癌症患者治疗的重要内容之一。TRP离子通道（TRPV1，TRPV4，TRPA1）在机体中枢神经系统中与痛觉的形成及传导密切相关。在中医理论的指导下，通络散结凝胶外用治疗癌痛经济、安全有效。初步研究表明通络散结凝胶外用治疗癌痛主要通过缓解局部疼痛、抑制局部骨组织破骨细胞的活性、降低外周血ICTP和BAP的水平及炎性细胞因子而实现。本课题组在此基础上，复制大鼠骨癌痛模型，采用四足动态承重测试系统、von frey测痛仪、热刺激测痛仪、Prodigy双能X线骨密度仪、免疫组化、ELISA等方法从疼痛行为学、影像学、骨密度、背根神经节TRPV1，TRPV4及TRPA1的表达、脊髓炎性介质IL-1β和IL-17基因的表达等不同层次深入研究通络散结凝胶外用治疗癌痛的中枢分子机制，为临床治疗癌痛提供科学依据。