Cannabinoids and Pain: Sites and Mechanisms of Action
Cannabinoids and Pain: Sites and Mechanisms of Action
复制标题
DOI：
10.1016/bs.apha.2017.05.003
复制
发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Finn, David P.
中科院分区：
文献类型：
--
作者：
Starowicz, Katarzyna;Finn, David P.
内源性大麻素系统由大麻素(1)受体(CB1R)和大麻素(2)受体(CB2R)、内源性大麻素配体(内源性大麻素)和代谢酶组成，存在于整个痛觉通路。内源性大麻素、植物大麻素和合成大麻素受体激动剂在急性、炎症性和神经病理性疼痛的动物模型中具有抗伤害效应。位于周围、脊髓或脊髓上的CB1R和CB2R是介导这些抗伤害效应的重要靶点。大麻素的镇痛作用机制可能包括抑制突触前神经递质和神经肽的释放，调节突触后神经元的兴奋性，激活下行抑制性痛觉通路，以及减少神经炎性信号。将大麻素的精神活性作用与其止痛作用分离的策略主要集中在外周限制性的CB1R激动剂、CB2R激动剂、内源性大麻素分解代谢或摄取的抑制剂，以及对大麻素的其他非CB1R/非CB2R靶标的调节，包括TRPV1、GPR55和PPAR。大量临床前证据支持大麻素作为潜在的止痛剂，临床研究证明了它们对各种疼痛障碍的有效性。
The endocannabinoid system, consisting of the cannabinoid(1) receptor (CB1R) and cannabinoid(2) receptor (CB2R), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CB1R and CB2R located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects. The mechanisms underlying the analgesic effects of cannabinoids likely include inhibition of presynaptic neurotransmitter and neuropeptide release, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pain pathway, and reductions in neuroinflammatory signaling. Strategies to dissociate the psychoactive effects of cannabinoids from their analgesic effects have focused on peripherally restricted CB1R agonists, CB2R agonists, inhibitors of endocannabinoid catabolism or uptake, and modulation of other non-CB1R/non-CB2R targets of cannabinoids including TRPV1, GPR55, and PPARs. The large body of preclinical evidence in support of cannabinoids as potential analgesic agents is supported by clinical studies demonstrating their efficacy across a variety of pain disorders.