Beltramo Massimiliano
Schering-Plough Research Institute, San Raffaele Biomedical Science Park, via Olgettina 58, 20132 Milan, Italy.
Mini Rev Med Chem. 2009 Jan;9(1):11-25. doi: 10.2174/138955709787001785.
Availability of selective pharmacological tools enabled a great advance of our knowledge of cannabinoid receptor 2 (CB2) role in pathophysiology. In particular CB2 emerged as an interesting target for chronic pain treatment as demonstrated by several studies on inflammatory and neuropathic preclinal pain models. The mechanisms at the basis of CB2-mediated analgesia are still controversial but data are pointing out in two main directions: an effect on inflammatory cells and/or an action on nociceptors and spinal cord relay centers. In this review will be described the second messenger pathways activated by CB2 agonists, the data underpinning the analgesic profile of CB2 selective agonists and the mechanisms invoked to explain their analgesic action. Finally the ongoing clinical trials and the potential issues for the development of a CB2 agonist drug will be examined.
选择性药理学工具的出现极大地推动了我们对大麻素受体2（CB2）在病理生理学中作用的认识。特别是，CB2已成为慢性疼痛治疗的一个有趣靶点，多项关于炎症性和神经性临床前疼痛模型的研究证明了这一点。CB2介导镇痛的基础机制仍存在争议，但数据主要指向两个方向：对炎症细胞的作用和/或对伤害感受器及脊髓中继中心的作用。在这篇综述中，将描述CB2激动剂激活的第二信使途径、支持CB2选择性激动剂镇痛谱的数据以及用于解释其镇痛作用的机制。最后，将探讨正在进行的临床试验以及开发CB2激动剂药物的潜在问题。
