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Cross-tolerance between spinal neostigmine and morphine in the rat
1Department of Anesthesiology, Tufts University School of Medicine, Baystate Medical Center, Springfield, MA 01199, USA. Stuart.Dunbar@bhs.org
British Journal of Anaesthesia
|August 20, 2003
Summary
Spinal neostigmine and morphine both cause tolerance to neostigmine. However, only morphine infusion led to cross-tolerance to morphine, indicating a unidirectional effect in pain relief mechanisms.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Management
Background:
- Cholinergic agonists, like neostigmine, are effective spinal analgesics.
- Investigating tolerance and cross-tolerance to spinal neostigmine and morphine is crucial for understanding pain relief mechanisms.
Purpose of the Study:
- To determine if spinal neostigmine induces tolerance.
- To examine if spinal neostigmine or morphine leads to cross-tolerance to morphine and neostigmine, respectively.
Main Methods:
- Rats received continuous intrathecal (i.t.) infusions of saline, morphine, or neostigmine.
- Antinociceptive effects were assessed via paw withdrawal latency to thermal stimuli.
- Dose-response curves were generated after daily infusions and challenge doses.
Main Results:
- Both neostigmine and morphine infusions induced tolerance to spinal neostigmine.
- Neostigmine infusion did not result in cross-tolerance to spinal morphine.
- Morphine infusion resulted in significant cross-tolerance to spinal neostigmine.
Conclusions:
- A unidirectional cross-tolerance from morphine to neostigmine was observed.
- Morphine's partial cholinergic mechanism may explain the observed unidirectional cross-tolerance.
- Findings suggest distinct pathways for spinal neostigmine and morphine antinociception.