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

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 arid 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 eotreatment. Key words: Opioid analgesics; Morphin; Ultra-low-dose naloxone; Tolerance/dependence attenuation; Mechanisms; AC/cAMP/PKA; Go/Gi-opioid receptor; Gs-opioid receptor; Filamin A