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Heme oxygenase type 2 modulates behavioral and molecular changes during chronic exposure to morphine
1Veterans Affairs Palo Alto Health Care System and Stanford University Department of Anesthesiology, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
Neuroscience
|October 29, 2003
Summary
Heme oxygenase type 2 (HO-2) is crucial for developing morphine tolerance and associated pain hypersensitivity. HO-2 null mice show reduced tolerance and mechanical allodynia, suggesting distinct mechanisms for tolerance and hypersensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- The heme oxygenase (HO) enzyme system plays a role in pain signaling.
- The specific role of the HO type 2 (HO-2) isozyme in opioid effects is not fully understood.
Purpose of the Study:
- To investigate the role of HO-2 in morphine analgesic tolerance.
- To examine HO-2's involvement in hyperalgesia and allodynia following morphine cessation.
Main Methods:
- Morphine treatment (5 days) in wild type and HO-2 null mutant mice.
- Assessment of analgesic tolerance, mechanical allodynia, and thermal hyperalgesia.
- Analysis of spinal cord mRNA expression for nitric oxide synthase type 1, NMDA receptor NMDAR1 subunit, and prodynorphin.
Main Results:
- Wild type mice developed tolerance, while HO-2 null mutants did not.
- HO-2 null mutants exhibited reduced mechanical allodynia after morphine cessation.
- Morphine treatment increased specific mRNA levels in wild type mice, but not in HO-2 null mutants.
Conclusions:
- HO-2 is essential for acquiring opioid tolerance and developing mechanical allodynia post-cessation.
- HO-2 influences gene regulation during morphine treatment.
- Mechanisms for analgesic tolerance and opioid-induced hypersensitivity appear distinct.