A.A. Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, 4 Bogomoletz Street, Kiev 01024, Ukraine.
Educational and Scientific Centre "Institute of Biology and Medicine", Taras Shevchenko Kiev National University, 2 Academician Glushkov Avenue, Kiev 03022, Ukraine.
Curr Neuropharmacol. 2018 Jan 30;16(2):137-150. doi: 10.2174/1570159X15666170424120802.
Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocannabinoid system may be a useful approach to pain alleviation. Classically, the system includes G protein-coupled receptors of the CB1 and CB2 subtypes and their endogenous ligands. More recently, several subtypes of the large superfamily of cation TRP channels have been coined as "ionotropic cannabinoid receptors", thus highlighting their role in cannabinoid signalling. Thus, the aim of this review was to explore the intimate connection between several "painful" TRP channels, endocannabinoids and nociceptive signalling.
Research literature on this topic was critically reviewed allowing us not only summarize the existing evidence in this area of research, but also propose several possible cellular mechanisms linking nociceptive and cannabinoid signaling with TRP channels.
We begin with an overview of physiology of the endocannabinoid system and its major components, namely CB1 and CB2 G protein-coupled receptors, their two most studied endogenous ligands, anandamide and 2-AG, and several enzymes involved in endocannabinoid biosynthesis and degradation. The role of different endocannabinoids in the regulation of synaptic transmission is then discussed in detail. The connection between the endocannabinoid system and several TRP channels, especially TRPV1-4, TRPA1 and TRPM8, is then explored, while highlighting the role of these same channels in pain signalling.
There is increasing evidence implicating several TRP subtypes not only as an integral part of the endocannabinoid system, but also as promising molecular targets for pain alleviation with the use of endo- and phytocannabinoids, especially when the function of these channels is upregulated under inflammatory conditions.
慢性疼痛是一个重大的临床问题，也是一种非常复杂的病理生理现象。越来越多的证据表明，靶向内源性大麻素系统可能是一种缓解疼痛的有效方法。经典上，该系统包括 CB1 和 CB2 亚型的 G 蛋白偶联受体及其内源性配体。最近，几种阳离子 TRP 通道大家族的亚型被称为“离子型大麻素受体”，从而强调了它们在大麻素信号传导中的作用。因此，本综述的目的是探讨几种“疼痛”TRP 通道、内源性大麻素和伤害性信号之间的密切联系。
对该主题的研究文献进行了批判性审查，使我们不仅能够总结该研究领域的现有证据，还能够提出将伤害性和大麻素信号与 TRP 通道联系起来的几种可能的细胞机制。
我们首先概述了内源性大麻素系统的生理学及其主要成分，即 CB1 和 CB2 G 蛋白偶联受体、它们两个最受研究的内源性配体，即花生四烯酸乙醇胺和 2-花生四烯酸甘油，以及参与内源性大麻素生物合成和降解的几种酶。然后详细讨论了不同内源性大麻素在调节突触传递中的作用。然后探讨了内源性大麻素系统与几种 TRP 通道（尤其是 TRPV1-4、TRPA1 和 TRPM8）之间的联系，同时强调了这些相同通道在疼痛信号中的作用。
越来越多的证据表明，几种 TRP 亚型不仅是内源性大麻素系统的组成部分，而且是使用内源性和植物性大麻素缓解疼痛的有前途的分子靶点，尤其是当这些通道在炎症条件下功能上调时。
