Vincenzi Fabrizio, Pasquini Silvia, Borea Pier Andrea, Varani Katia
Department of Translational Medicine and for Romagna, Pharmacology Section, University of Ferrara, 44121 Ferrara, Italy.
University of Ferrara, 44121 Ferrara, Italy.
Int J Mol Sci. 2020 Nov 18;21(22):8710. doi: 10.3390/ijms21228710.
Adenosine is a purine nucleoside, responsible for the regulation of multiple physiological and pathological cellular and tissue functions by activation of four G protein-coupled receptors (GPCR), namely A, A, A, and A adenosine receptors (ARs). In recent years, extensive progress has been made to elucidate the role of adenosine in pain regulation. Most of the antinociceptive effects of adenosine are dependent upon AAR activation located at peripheral, spinal, and supraspinal sites. The role of AAR and AAR is more controversial since their activation has both pro- and anti-nociceptive effects. AAR agonists are emerging as promising candidates for neuropathic pain. Although their therapeutic potential has been demonstrated in diverse preclinical studies, no AR ligands have so far reached the market. To date, novel pharmacological approaches such as adenosine regulating agents and allosteric modulators have been proposed to improve efficacy and limit side effects enhancing the effect of endogenous adenosine. This review aims to provide an overview of the therapeutic potential of ligands interacting with ARs and the adenosinergic system for the treatment of acute and chronic pain.
腺苷是一种嘌呤核苷，通过激活四种G蛋白偶联受体（GPCR），即A1、A2A、A2B和A3腺苷受体（ARs），负责调节多种生理和病理细胞及组织功能。近年来，在阐明腺苷在疼痛调节中的作用方面取得了广泛进展。腺苷的大多数抗伤害感受作用依赖于位于外周、脊髓和脊髓上部位的A1AR激活。A2AR和A2BR的作用更具争议性，因为它们的激活既有促伤害感受作用，也有抗伤害感受作用。A3AR激动剂正成为治疗神经性疼痛的有前景的候选药物。尽管它们的治疗潜力已在各种临床前研究中得到证实，但迄今为止尚无AR配体进入市场。迄今为止，已提出了诸如腺苷调节剂和变构调节剂等新型药理学方法，以提高疗效并限制副作用，增强内源性腺苷的作用。本综述旨在概述与ARs相互作用的配体以及腺苷能系统在治疗急性和慢性疼痛方面的治疗潜力。
