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慢性痛是困扰临床的一大顽疾,关于慢性痛机制的研究和新型镇痛药物的研发具有重要意义。十多年来,本研究组围绕慢性痛外周敏化形成的关键分子——瞬时受体电位香草酸亚型1(transient receptor potential vanilloid type 1,TRPV1),对其敏化和膜定位机制进行了系列研究,揭示了蛋白激酶PKD1(protein kinase D1)、Cdk5(cyclin-dependent kinase 5)和LIMK(LIM-motif containing kinase)在炎症诱发热痛敏中的作用及其对TRPV1的功能调控,并据此开发出了一系列具有镇痛作用的Tat穿膜肽。本综述还围绕研究组近期工作所揭示的参与痛感觉和痛情绪相互作用的关键脑区——前额叶皮质的前边缘皮质亚区,对TRPV1在其中的可能作用进行了探讨。此外本综述也对研究组在改进TRPV1靶向药物,提高其镇痛疗效,降低副作用方面的工作进行了简要总结和回顾。
Chronic pain is a major clinical problem plagued by chronic pain on the mechanism of research and development of new analgesic drugs is of great significance. For more than a decade, our group focused on the sensitization and membrane localization mechanism of transient receptor potential vanilloid type 1 (TRPV1), a key molecule formed by peripheral sensitization of chronic pain. Series of studies have revealed the role of protein kinase D1, cyclin-dependent kinase 5 (LIMK) and LIMK (LIM-motif containing kinase) in inflammation-induced hyperalgesia and their functional regulation of TRPV1 This has resulted in a series of Tat penetrating peptides that have analgesic effects. This review also explored the possible role of TRPV1 in the forefront cortical subregion of the prefrontal cortex, a key brain area involved in the pain-relief interaction as revealed by recent work by the group. In addition, this review also briefly summarized and reviewed the work of the research group in improving TRPV1-targeted drugs, improving their analgesic efficacy and reducing side effects.