小剂量纳洛酮联合阿片类药物应用的研究进展

Progress in the study of combining opioid analgesics and nitra4ow-dose naloxone

背景阿片类镇痛药在临床应用有着重要的地位，但有恶心、呕吐、瘙痒、呼吸抑制等不可忽视副作用，长期应用还可产生耐受和依赖。有研究表明，阿片类镇痛药联合应用小剂量的阿片类受体拮抗剂可以明显增强吗啡等阿片类镇痛药的效能，并且同时减弱由其产生的副作用以及耐受和依赖。目的拟通过综述的方式，系统地阐述小剂量纳洛酮联合应用阿片类药物的研究现状以及进展，为今后该方向的研究提供参考，进而启发新的研究思路。内容对阿片类镇痛药联合小剂量纳洛酮应用的基础及临床研究现状和进展以及小剂量纳洛酮增强阿片类镇痛药的镇痛作用、减轻其副作用及耐受和依赖的形成机制进行综述。趋向从近期研究可见，该方向的研究已不仅限于观察小剂量纳洛酮与吗啡的联合应用所产生的作用，小剂量纳洛酮和其他阿片类药物联合应用的研究也逐步展开，并有越来越多的研究者对二者联合应用所产生的作用机制进行了更为深入的探讨．

Background Opioid analgesics play an important role in clinical settings. However, they also have some side effects, such as nausea, vomiting, pruritus, respiratory depression and so on, which could limit their wide use. Recently, lots of preclinical and clinical studies have demonstrated that cotreatments with extremely small dose of opioid receptor antagonists can markedly enhance the efficacy of opioid analgesics and simultaneously reduce side effects induced by opioids including tolerance and dependence. Objective This article intends to review the progress in the study of the clinical application of opioid analgesics combined with ultra-low-dose naloxone in order to inspire some new research ideas： Content This article is a review of the progress in the preclinical and clinical studies of combining opioid analgesics and ultra-low-dose naloxone. In the mean time, we set out the probable mechanisms that could account for the enhancement of opioids＂ analgesic potency and attenuation of side effects, tolerance and dependence, which induced by opioids, during cotreatment with opioids and naloxone. Trend Recently, directions of the research are not limited to observation of the effectiveness in combining ultra-low -dose naloxone and morphine as well as in company with other opioids. More and more researchers are eager to concern about the mechanism of this cotreatment.