Department of Pharmacology, Southern Illinois University School of Medicine Springfield, IL 62702, USA.
Life Sci. 2013 Mar 19;92(8-9):415-24. doi: 10.1016/j.lfs.2012.08.010. Epub 2012 Aug 14.
Since cloning and characterizing the first nociceptive ion channel Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1), other TRP channels involved in nociception have been cloned and characterized, which include TRP Vanilloid 2 (TRPV2), TRP Vanilloid 3 (TRPV3), TRP Vanilloid 4 (TRPV4), TRP Ankyrin 1 (TRPA1) and TRP Melastatin 8 (TRPM8), more recently TRP Canonical 1, 5, 6 (TRPC1, 5, 6), TRP Melastatin 2 (TRPM2) and TRP Melastatin 3 (TRPM3). These channels are predominantly expressed in C and Aδ nociceptors and transmit noxious thermal, mechanical and chemical sensitivities. TRP channels are modulated by pro-inflammatory mediators, neuropeptides and cytokines. Significant advances have been made targeting these receptors either by antagonists or agonists to treat painful conditions. In this review, we will discuss TRP channels as targets for next generation analgesics and the side effects that may ensue as a result of blocking/activating these receptors, because they are also involved in physiological functions such as release of vasoactive neuropeptides and regulation of vascular tone, maintenance of the body temperature, gastrointestinal motility, urinary bladder control, etc.
自从克隆和鉴定第一个伤害性离子通道瞬时受体电位香草素 1（TRPV1）以来，其他参与伤害感受的 TRP 通道也已被克隆和鉴定，包括 TRPV2、TRPV3、TRPV4、TRPA1 和 TRPM8，最近还包括 TRPV1、TRPC1、5、6、TRPM2 和 TRPM3。这些通道主要在 C 和 Aδ 伤害感受器中表达，并传递有害的热、机械和化学敏感性。TRP 通道受促炎介质、神经肽和细胞因子的调节。通过拮抗剂或激动剂靶向这些受体已取得重大进展，以治疗疼痛状况。在这篇综述中，我们将讨论 TRP 通道作为下一代镇痛药的靶点，以及阻断/激活这些受体可能产生的副作用，因为它们还参与生理功能，如血管活性神经肽的释放和血管张力的调节、体温的维持、胃肠道蠕动、膀胱控制等。
