Microglial Cannabinoid CB2 Receptors in Pain Modulation

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2348
• Main Authors: Xu, Kangtai, Wu, Yifei, Tian, Zhuangzhuang, Xu, Yuanfan, Wu, Chaoran, Wang, Zilong
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.02.2023; MDPI
• Subjects: Agonists; Analgesia; Analgesics; Brain research; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Cannabinoids; CB2 receptors; Central nervous system; Chronic pain; Enzymes; Immune system; Kinases; Ligands; Memory; Microglia; Neural networks; Neuropeptides; Pain; Pain perception; pathological pain; Peptides; Physiology; Quality of life; Receptor mechanisms; Review; Side effects; Signal transduction; Spinal cord; the endocannabinoid system
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032348

Pain, especially chronic pain, can strongly affect patients’ quality of life. Cannabinoids ponhave been reported to produce potent analgesic effects in different preclinical pain models, where they primarily function as agonists of Gi/o protein-coupled cannabinoid CB1 and CB2 receptors. The CB1 receptors are abundantly expressed in both the peripheral and central nervous systems. The central activation of CB1 receptors is strongly associated with psychotropic adverse effects, thus largely limiting its therapeutic potential. However, the CB2 receptors are promising targets for pain treatment without psychotropic adverse effects, as they are primarily expressed in immune cells. Additionally, as the resident immune cells in the central nervous system, microglia are increasingly recognized as critical players in chronic pain. Accumulating evidence has demonstrated that the expression of CB2 receptors is significantly increased in activated microglia in the spinal cord, which exerts protective consequences within the surrounding neural circuitry by regulating the activity and function of microglia. In this review, we focused on recent advances in understanding the role of microglial CB2 receptors in spinal nociceptive circuitry, highlighting the mechanism of CB2 receptors in modulating microglia function and its implications for CB2 receptor- selective agonist-mediated analgesia.