Annexin1调节瞬时感受器电位香草素受体1敏感性介导抗炎症痛的机制研究

项目名称： Annexin1调节瞬时感受器电位香草素受体1敏感性介导抗炎症痛的机制研究

项目编号： No.81200863

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 裴磊

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 外周炎症或神经损伤引起的慢性痛一直是临床治疗的难点，根据内源性镇痛物质如阿片类和大麻素开发的镇痛药虽然有明显疗效，但长期使用会产生成瘾性和副作用。因此，开发新的镇痛药物十分必要。我们近期工作发现：在完全福氏佐剂诱导的慢性炎症痛大鼠模型，介导糖皮质激素抗炎的中介分子Annexin1(ANXA1)呈现表达上调，且能通过甲酰肽样受体1（FPR2/ALX）在背根神经节（DRGs）水平发挥抗炎症痛作用。在此基础上，本研究拟在离体与在体炎症痛模型，外源给予ANXA1刺激后，通过观察神经元TRPV1的电流，胞内磷脂酶C的活性、钙离子浓度、钙调蛋白与TRPV1的相互作用以及脊髓背角神经元放电，进一步研究：ANXA1-FPR2/ALX胞内信号对TRPV1敏感性的调节介导抗伤害性作用，以阐明ANXA1抗炎症痛的细胞分子机制，为探寻新的内源性镇痛物质及开发镇痛药提供理论依据与分子靶标。

中文关键词： Annexin 1；甲酰肽样受体1；瞬时感受器电位香草素受体1；敏感性；伤害性感受

英文摘要： Chronic pain caused by peripheral inflammation or nerve damage has always been the difficulty for clinical treatment. Currently developed analgesic drugs from the endogenous analgesic substances, such as opioids and cannabinoids, have shown therapeutic effects, but evidences showed that long-term use of these drugs produced addiction and side effects. Therefore, exploring new analgesic drugs is necessary. Our recent study have demonstrated that Annexin1 (ANXA1), an anti-inflammatory mediator of glucocoticoid, exerts anti-nociceptive effect through formyl peptide receptor like 1 (FPR2/ALX)) at the dorsal root ganglia (DRGs) level in Complete Freund's adjuvant-induced rat model of chronic inflammatory pain. Based on the previous work, the proposed study will perform in vitro and in vivo experiments on the inflammatory pain model to elucidate the cellular and molecular mechanisms of ANXA1's anti-nociceptive effects. Specifically, after applying exogenous ANXA1 into the DRGs neurons, TRPV1 current, phospholipase C activity, intracellular calcium ion, the interaction between calmodulin and TRPV1, the firing of spinal dorsal horn neurons will be studied. Then, ANXA1-FPR2/ALX intracellular signals and its regulative role on the TRPV1 function will be ellucidated. Our study will provide substantial evidence and possibl

英文关键词： Annexin 1；Formyl peptide receptor like-1；Transient receptor potential vanilloid 1；Sensitivity；Nociception