Zhou Jie, Ma Ruijie, Jin Ying, Fang Junfan, Du Junying, Shao Xiaomei, Liang Yi, Fang Jianqiao
Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
Department of Rehabilitation in Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China.
Exp Ther Med. 2021 Sep;22(3):1004. doi: 10.3892/etm.2021.10437. Epub 2021 Jul 15.
Opioids are considered the most effective analgesics for the treatment of both acute and chronic pain. However, prolonged opioid use can induce a certain level of tolerance to its analgesic effects, leading to a reduction in its effectiveness, addiction and abuse. A better understanding of the mechanisms underlying opioid tolerance may provide insights into this phenomenon and aid in the development of novel methods to combat the side effects of opioid tolerance. The present review focused on two major contributors to tolerance, opioid receptors and inflammatory mediators. The molecular mechanisms involved in the desensitization of the opioid receptors were briefly described, including their phosphorylation, internalisation and recycling. Subsequently, the effects of Toll like receptor 4/NOD-like receptor family pyrin domain containing 3-mediated proinflammatory responses in opioid tolerance were discussed, aiming in supporting the identification of novel therapeutic targets.
阿片类药物被认为是治疗急性和慢性疼痛最有效的镇痛药。然而，长期使用阿片类药物会导致对其镇痛效果产生一定程度的耐受性，从而导致其有效性降低、成瘾和滥用。更好地理解阿片类药物耐受性的潜在机制可能有助于深入了解这一现象，并有助于开发新方法来对抗阿片类药物耐受性的副作用。本综述重点关注耐受性的两个主要因素，即阿片受体和炎症介质。简要描述了阿片受体脱敏所涉及的分子机制，包括其磷酸化、内化和再循环。随后，讨论了Toll样受体4/含核苷酸结合寡聚化结构域样受体家族吡咯结构域蛋白3介导的促炎反应在阿片类药物耐受性中的作用，旨在支持确定新的治疗靶点。
