Department of Physiology and Pharmacology, Inflammation Research Network-Snyder Institute for Chronic Diseases and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada.
Drugs. 2021 Jan;81(1):7-27. doi: 10.1007/s40265-020-01429-2.
The transient receptor potential vanilloid-1 (TRPV1) is a non-specific cation channel known for its sensitivity to pungent vanilloid compound (i.e. capsaicin) and noxious stimuli, including heat, low pH or inflammatory mediators. TRPV1 is found in the somatosensory system, particularly primary afferent neurons that respond to damaging or potentially damaging stimuli (nociceptors). Stimulation of TRPV1 evokes a burning sensation, reflecting a central role of the channel in pain. Pharmacological and genetic studies have validated TRPV1 as a therapeutic target in several preclinical models of chronic pain, including cancer, neuropathic, postoperative and musculoskeletal pain. While antagonists of TRPV1 were found to be a valuable addition to the pain therapeutic toolbox, their clinical use has been limited by detrimental side effects, such as hyperthermia. In contrast, capsaicin induces a prolonged defunctionalisation of nociceptors and thus opened the door to the development of a new class of therapeutics with long-lasting pain-relieving effects. Here we review the list of TRPV1 agonists undergoing clinical trials for chronic pain management, and discuss new indications, formulations or combination therapies being explored for capsaicin. While the analgesic pharmacopeia for chronic pain patients is ancient and poorly effective, modern TRPV1-targeted drugs could rapidly become available as the next generation of analgesics for a broad spectrum of pain conditions.
瞬时受体电位香草酸亚型 1（TRPV1）是一种非特异性阳离子通道，对辛辣香草化合物（即辣椒素）和有害刺激物（包括热、低 pH 值或炎症介质）敏感。TRPV1 存在于躯体感觉系统中，特别是对伤害性或潜在伤害性刺激有反应的初级传入神经元（伤害感受器）。TRPV1 的刺激会引起烧灼感，反映出该通道在疼痛中的核心作用。药理学和遗传学研究已经证实 TRPV1 是几种慢性疼痛的临床前模型中的治疗靶点，包括癌症、神经性、术后和肌肉骨骼疼痛。虽然 TRPV1 的拮抗剂被发现是疼痛治疗工具箱的一个有价值的补充，但它们的临床应用受到有害副作用的限制，例如发热。相比之下，辣椒素会导致伤害感受器长期失能，从而为开发一类具有持久止痛效果的新型治疗药物开辟了道路。本文综述了正在进行临床试验以用于慢性疼痛管理的 TRPV1 激动剂，讨论了正在探索的辣椒素的新适应症、制剂或联合治疗。虽然慢性疼痛患者的镇痛药物库历史悠久且效果不佳，但新型 TRPV1 靶向药物可能很快成为新一代广谱疼痛治疗药物。
