Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: a strategy to increase opioid antinociception.
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.
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1069, USA.
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D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D005727:Ganglia, Spinal / Q000502:physiology / Q000503:physiopathology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009020:Morphine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000517:prevention & control*; D018408:Patch-Clamp Techniques; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D008164:Luminescent Proteins; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D009020:Morphine