Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a ...

The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP), an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl/h) for 3 d...

background: chronic use of opioids usually results in physical dependence. the underlying mechanisms for this dependence are still being evaluated. transient receptor potential vanilloid type 1 (trpv1) are important receptors of pain perception. their role during opioid dependence has not been studied well. the aim of this study was to evaluate the effect of morphine-dependence on the expressio...

Agonist-induced receptor phosphorylation is an initial step in opioid receptor desensitization, a molecular mechanism of opioid tolerance and dependence. Our previous research suggested that agonist-induced d-opioid receptor (DOR) phosphorylation occurs at the receptor carboxyl terminal domain. The current study was carried out to identify the site of DOR phosphorylation during agonist stimulat...

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provid...

BACKGROUND This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir. METHODS The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphin...

Background: Acute and chronic pain is prevalent in patients with opioid dependence. Lack of knowledge concerning the complex relationship between pain, opioid use, and withdrawal syndrome can account for the barriers encountered for pain management. This study was designed to evaluate the efficacy of sublingual (SL) buprenorphine for post-operative analgesia, compared with intravenous (IV) morp...

COVER Immunostained fl uorescence microscopy image of a biomarker of endogenous withdrawal (phosphorylated extracellular regulated kinase, red) that increases in mouse spinal cord neurons (green) during opioid receptor blockade (image width: 250 micrometers). Infl ammation or injury to the skin causes μ-opioid receptors to become constitutively active, which leads to long-term relief from chron...

Throughout the long history of opioid drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeu...