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 language | English |
---|---|
Pages (from-to) | 614-622 |
Number of pages | 9 |
Journal | Addiction Biology |
Volume | 18 |
Issue number | 4 |
DOIs | |
Publication status | Published - Jul 2013 |
Externally published | Yes |
Keywords
- Fentanyl
- mouse
- neuropathic pain
- opioid tolerance
- spinal cord
- μ-opioid receptor