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- Title
Possible involvement of prolonging spinal µ-opioid receptor desensitization in the development of antihyperalgesic tolerance to µ-opioids under a neuropathic pain-like state.
- Authors
Narita, Minoru; Imai, Satoshi; Nakamura, Atsushi; Ozeki, Ayumi; Asato, Megumi; Rahmadi, Mahardian; Sudo, Yuka; Hojo, Minoru; Uezono, Yasuhito; Devi, Lakshmi A; Kuzumaki, Naoko; Suzuki, Tsutomu
- 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.
- Publication
Addiction biology, 2013, Vol 18, Issue 4, p614
- ISSN
1369-1600
- Publication type
Journal Article
- DOI
10.1111/j.1369-1600.2011.00354.x