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

Minoru Narita, Satoshi Imai, Atsushi Nakamura, Ayumi Ozeki, Megumi Asato, Mahardian Rahmadi, Yuka Sudo, Minoru Hojo, Yasuhito Uezono, Lakshmi A. Devi, Naoko Kuzumaki, Tsutomu Suzuki

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)614-622
Number of pages9
JournalAddiction Biology
Volume18
Issue number4
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • Fentanyl
  • mouse
  • neuropathic pain
  • opioid tolerance
  • spinal cord
  • μ-opioid receptor

Fingerprint

Dive into the research topics of 'Possible involvement of prolonging spinal μ-opioid receptor desensitization in the development of antihyperalgesic tolerance to μ-opioids under a neuropathic pain-like state'. Together they form a unique fingerprint.

Cite this