Roberts Louise A, Connor Mark
Pain Management Research Institute, Kolling Institute, Level 4, Main Block, University of Sydney at Royal North Shore Hospital, E25. St. Leonards, NSW 2065, Sydney, Australia.
Recent Pat CNS Drug Discov. 2006 Jan;1(1):65-76. doi: 10.2174/157488906775245309.
The vanilloid receptor (TRPV1) is a member of the transient receptor potential family of ion channels that is highly expressed in nociceptive primary afferent sensory neurons. TRPV1 is a voltage-dependent cation channel, which can be activated at physiological membrane potentials by stimuli including noxious heat (>42 degrees), capsaicin, hydrogen ions and anandamide. Activation of TRPV1 results in release of neurotransmitters from peripheral and central nerve terminals, resulting in pain and inflammation. Endogenous inflammatory mediators also promote activation of TRPV1. Studies in TRPV1 null mice reveal that responses to noxious heat stimuli are normal but the development of thermal hyperalgesia is abolished. Several TRPV1 antagonists have recently been developed and reported to alleviate or reverse mechanical and thermal hyperalgesia associated with inflammatory pain. This review will examine the development of patented TRPV1 antagonists as a potential clinical treatment for the alleviation of pain associated with hyperalgesia and inflammation.
香草酸受体（TRPV1）是瞬时受体电位离子通道家族的成员，在伤害性初级传入感觉神经元中高度表达。TRPV1是一种电压依赖性阳离子通道，在生理膜电位下可被包括有害热（>42摄氏度）、辣椒素、氢离子和花生四烯酸乙醇胺在内的刺激激活。TRPV1的激活导致神经递质从外周和中枢神经末梢释放，从而引起疼痛和炎症。内源性炎症介质也促进TRPV1的激活。对TRPV1基因敲除小鼠的研究表明，对有害热刺激的反应正常，但热痛觉过敏的发展被消除。最近已开发出几种TRPV1拮抗剂，并报道它们可减轻或逆转与炎性疼痛相关的机械性和热痛觉过敏。本综述将探讨专利TRPV1拮抗剂作为缓解与痛觉过敏和炎症相关疼痛的潜在临床治疗方法的发展情况。
