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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Buprenorphine-induced hyperalgesia in the rat
Elzbieta P Wala1, Joseph R Holtman
1Department of Anesthesiology, University of Kentucky, Lexington, KY 40536-0293, USA. epwala@uky.edu
European Journal of Pharmacology
|December 1, 2010
Summary
Buprenorphine, an opioid analgesic, can cause pain sensitivity at ultra-low doses but provides pain relief at higher doses. This effect involves NMDA receptors and may impact chronic pain management.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Research
Background:
- Opioids can paradoxically increase pain sensitivity (opioid-induced hyperalgesia), counteracting their analgesic effects.
- Buprenorphine, a unique opioid, has a better safety profile than typical mu-opioid agonists.
- The potential for buprenorphine-induced hyperalgesia remains largely unknown.
Purpose of the Study:
- To investigate buprenorphine's effects on pain sensitivity after acute and repeated administration in rats.
- To explore the role of NMDA receptors in buprenorphine-induced hyperalgesia.
- To determine if buprenorphine's analgesic efficacy diminishes with repeated dosing or prior hyperalgesia.
Main Methods:
- Utilized a rat model of thermal nociception (tail-flick test).
- Administered acute and repeated doses of buprenorphine (high and ultra-low).
- Investigated the effects of ketamine, an NMDA receptor antagonist, on buprenorphine-induced hyperalgesia.
Main Results:
- Buprenorphine demonstrated dose-dependent antinociception.
- Repeated buprenorphine dosing led to tolerance and subsequent enhanced pain sensitivity (delayed hyperalgesia).
- Ultra-low dose buprenorphine caused immediate hyperalgesia, both reversed by ketamine, indicating NMDA receptor involvement.
Conclusions:
- Buprenorphine exhibits bimodal effects: pronociceptive at ultra-low doses and antinociceptive at higher doses.
- NMDA receptor antagonism mitigates buprenorphine-induced hyperalgesia.
- Buprenorphine's potential for hyperalgesia warrants consideration for chronic pain management strategies.
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