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Published on: November 11, 2013
When it comes to opiates, just say NO.
1Department of Neurology and The Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. pasterng@mskcc.org
The Journal of Clinical Investigation
|November 3, 2007
Summary
Chronic morphine use causes tolerance by converting nitric oxide (NO) into peroxynitrite. This molecule nitrates proteins in the spinal cord, suggesting peroxynitrite regulation could manage opiate tolerance.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Opiate analgesics like morphine are used for chronic pain but can lead to tolerance and dependence, narrowing the therapeutic index.
- Previous research indicated that blocking the N-methyl-D-aspartate receptor and nitric oxide (NO) signaling pathways prevents morphine tolerance.
Discussion:
- This study demonstrates that in mice, chronic morphine administration leads to NO conversion into peroxynitrite.
- Peroxynitrite accumulation results in tyrosine nitration of proteins within the spinal cord.
Key Insights:
- Morphine tolerance is linked to the conversion of NO to peroxynitrite.
- Peroxynitrite formation and subsequent protein nitration in the spinal cord are key mechanisms in opiate tolerance.
Outlook:
- Targeting peroxynitrite may offer a novel strategy for managing opiate-induced tolerance.
- Further research into peroxynitrite regulation could lead to improved pain management therapies.
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