Cui Di, Zhang Yuanyuan, Zhang Mingyue
Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.
IBRO Neurosci Rep. 2023 Dec 1;16:43-50. doi: 10.1016/j.ibneur.2023.11.005. eCollection 2024 Jun.
Pain highly impacts the quality of life of patients. Morphine is used for pain treatment; however, its side effects, especially morphine tolerance, limit its use in the clinic. The problem of morphine tolerance has plagued health workers and patients for years. Unfortunately, the exact mechanism of morphine tolerance has not been fully clarified. The mechanisms of morphine tolerance that are currently being studied may include μ-opioid receptor (MOR) desensitization and internalization, mitogen-activated protein kinase (MAPK) pathway activation and crosstalk, the effects of microglia and the increase in inflammatory factors. Morphine tolerance can be alleviated by improving the pathophysiological changes that lead to morphine tolerance. Previous studies have shown that a cannabinoid type 2 (CB2) receptor agonist could attenuate morphine tolerance in a variety of animal models. Many studies have shown an interaction between the cannabinoid system and the opioid system. The CB2 receptor may modulate the effect of morphine through a pathway that is common to the MOR, since both receptors are G protein-coupled receptors (GPCRs). This study introduces the potential mechanism of morphine tolerance and the effect of CB2 receptor agonists on reducing morphine tolerance, which can provide new ideas for researchers studying morphine and provide beneficial effects for patients suffering from morphine tolerance.
疼痛对患者的生活质量有很大影响。吗啡用于疼痛治疗；然而，其副作用，尤其是吗啡耐受性，限制了它在临床上的应用。吗啡耐受性问题多年来一直困扰着医护人员和患者。不幸的是，吗啡耐受性的确切机制尚未完全阐明。目前正在研究的吗啡耐受性机制可能包括μ-阿片受体（MOR）脱敏和内化、丝裂原活化蛋白激酶（MAPK）途径激活和相互作用、小胶质细胞的作用以及炎症因子增加。通过改善导致吗啡耐受性的病理生理变化，可以减轻吗啡耐受性。先前的研究表明，2型大麻素（CB2）受体激动剂可在多种动物模型中减弱吗啡耐受性。许多研究表明大麻素系统与阿片系统之间存在相互作用。CB2受体可能通过一条与MOR共有的途径调节吗啡的作用，因为这两种受体都是G蛋白偶联受体（GPCRs）。本研究介绍了吗啡耐受性的潜在机制以及CB2受体激动剂对降低吗啡耐受性的作用，可为研究吗啡的研究人员提供新思路，并为患有吗啡耐受性的患者带来益处。
