Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: a strategy to increase opioid antinociception.

Abstract

To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the mu-opioid receptor (muOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in muOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-muOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca(2+) channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.

• Authors: Y Xu, Y Gu, G-Y Xu, P Wu, G-W Li, L-Y M Huang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 10 Pg. 6204-9 (May 13 2003) ISSN: 0027-8424 [Print] United States
• PMID: 12719538 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Luminescent Proteins
• Receptors, Opioid
• Recombinant Fusion Proteins
• Recombinant Proteins
• Green Fluorescent Proteins
• Morphine

Topics

• Animals
• Dependovirus (genetics)
• Ganglia, Spinal (physiology, physiopathology)
• Gene Transfer Techniques
• Green Fluorescent Proteins
• Luminescent Proteins (genetics)
• Membrane Potentials (physiology)
• Models, Neurological
• Morphine (pharmacology)
• Neurons, Afferent (drug effects, physiology)
• Pain (prevention & control)
• Patch-Clamp Techniques
• Plasmids
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid (genetics, physiology)
• Recombinant Fusion Proteins (metabolism)
• Recombinant Proteins (metabolism)