Transgene-mediated enkephalin expression attenuates signs of naloxone-precipitated morphine withdrawal in rats with neuropathic pain.

Abstract

Chronic morphine exposure induces physical dependence and tolerance. Previous studies have shown that there is a decrease in met-enkephalin levels in states of morphine physical dependence, and that increasing enkephalin during opiate physical withdrawal ameliorates the severity of the morphine withdrawal syndrome. In order to investigate the role of spinal opioid peptide in the phenomenon of naloxone-precipitated withdrawal we examined the effect of herpes simplex virus vector-mediated overexpression of proenkephalin in lumbar dorsal root ganglia in rats with neuropathic pain treated with morphine. The morphine physical dependence was induced by chronic administration of intraperitoneal (IP) morphine for 2 weeks. Rats with neuropathic pain inoculated subcutaneously with the vector-mediated overexpression of proenkephalin showed a significant reduction in jumps, 'wet-dog' shakes, diarrhea and ptosis precipitated by naloxone after 2 weeks of morphine treatment. The global withdrawal score was also reduced significantly by vector-mediated overexpression of proenkephalin. These studies demonstrate a role for opioid peptide in the spinal cord in mediating some of the withdrawal response.

• Authors: Shuanglin Hao, Jian Hu, David J Fink
• Journal: Behavioural brain research (Behav Brain Res) Vol. 197 Issue 1 Pg. 84-9 (Jan 30 2009) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 18761380 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Analgesics, Opioid
• Enkephalins
• Protein Precursors
• proenkephalin
• Naloxone
• Morphine

Topics

• Analgesics, Opioid (therapeutic use)
• Animals
• Disease Models, Animal
• Enkephalins (genetics, metabolism)
• Ganglia, Spinal (metabolism, pathology)
• Gene Transfer Techniques
• Genetic Vectors
• Ligation
• Lumbar Vertebrae
• Male
• Morphine (therapeutic use)
• Morphine Dependence (metabolism, prevention & control)
• Naloxone
• Pain Threshold (physiology)
• Peripheral Nervous System Diseases (drug therapy, metabolism, pathology)
• Protein Precursors (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Simplexvirus (genetics)
• Spinal Nerve Roots (metabolism, pathology)
• Substance Withdrawal Syndrome (metabolism, prevention & control)
• Transgenes (genetics, physiology)