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Peripheral blockade of topical morphine tolerance by ketamine
Y A Kolesnikov1, G W Pasternak
1Department of Anesthesiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
European Journal of Pharmacology
|July 28, 1999
Summary
Topical ketamine prevents and reverses morphine tolerance by acting on peripheral N-methyl-D-aspartate (NMDA) receptors. This suggests potential clinical applications for NMDA receptor antagonists in pain management.
Area of Science:
- Pharmacology
- Pain Management
- Neuroscience
Background:
- Repeated topical morphine administration leads to tolerance within three days.
- Ketamine alone shows minimal effect in pain assays.
Purpose of the Study:
- To investigate the effect of topical ketamine on morphine tolerance.
- To explore the role of peripheral N-methyl-D-aspartate (NMDA) receptors in morphine tolerance.
Main Methods:
- Daily topical administration of morphine and ketamine.
- Radiant heat tailflick assay to measure pain response.
- Dose-dependent administration of topical ketamine with morphine.
Main Results:
- Topical ketamine prevented the development of morphine tolerance in a dose-dependent manner.
- Topical ketamine reversed pre-existing morphine tolerance.
- Ketamine alone had little effect on pain response.
Conclusions:
- Peripheral NMDA receptors mediate topical morphine tolerance.
- Topical NMDA receptor antagonists may offer clinical potential for managing opioid tolerance.