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Addict Biol. 2013 Jul;18(4):614-22. doi: 10.1111/j.1369-1600.2011.00354.x. Epub 2011 Aug 4.

Possible involvement of prolonging spinal µ-opioid receptor desensitization in the development of antihyperalgesic tolerance to µ-opioids under a neuropathic pain-like state.

Author information

  • 1Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan. narita@hoshi.ac.jp

Abstract

In the present study, we investigated the possible development of tolerance to the antihyperalgesic effect of µ-opioid receptor (MOR) agonists under a neuropathic pain-like state. Repeated treatment with fentanyl, but not morphine or oxycodone, produced a rapid development of tolerance to its antihyperalgesic effect in mice with sciatic nerve ligation. Like the behavioral study, G-protein activation induced by fentanyl was significantly reduced in membranes obtained from the spinal cord of nerve-ligated mice with in vivo repeated injection of fentanyl. In β-endorphin-knockout mice with nerve ligation, developed tolerance to the antihyperalgesic effect of fentanyl was abolished, and reduced G-protein activation by fentanyl after nerve ligation with fentanyl was reversed to the normal level. The present findings indicate that released β-endorphin within the spinal cord may be implicated in the rapid development of tolerance to fentanyl under a neuropathic pain-like state.

© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

PMID:
21812868
[PubMed - indexed for MEDLINE]
PMCID:
PMC3852690
Free PMC Article

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