Enhanced peripheral analgesia using virally mediated gene transfer of the mu-opioid receptor in mice.
BACKGROUND
The use of opioids to treat pain is often limited by side effects mediated through the central nervous system. The current study used a recombinant herpes simplex virus type 1 to increase expression of the mu-opioid receptor (muOR) in primary afferent neurons. The goal of this strategy was to enhance peripheral opioid analgesia.


METHODS
Cutaneous inoculation with herpes simplex virus containing muOR complementary DNA (cDNA) in antisense (SGAMOR) or sense (SGMOR) orientation relative to a constitutive promoter, or complementary DNA for Escherichia coli lac Z gene as a control virus (SGZ) was used to modify the levels of muOR in primary afferents. The effects of altered muOR levels on peripheral analgesia were then examined.


RESULTS
At 4 weeks after SGAMOR and SGMOR infection, decreased and increased muOR immunoreactivity was observed in ipsilateral dorsal hind paw skin, lumbar dorsal root ganglion cells, and superficial dorsal horns, respectively, compared with SGZ. This change in muOR expression in mice by SGAMOR and SGMOR was accompanied at the behavioral level with a rightward and leftward shift in the loperamide dose-response curve, respectively, compared with SGZ.


CONCLUSIONS
This gene therapy approach may provide an innovative strategy to enhance peripheral opioid analgesia for the treatment of pain in humans, thereby minimizing centrally mediated opioid side effects such as sedation and addiction.
Zhang
Guohua
G
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina 29208, USA.
Mohammad
Husam
H
Peper
Brad D
BD
Raja
Srinivasa
S
Wilson
Steven P
SP
Sweitzer
Sarah M
SM
D000698:Analgesia / Q000379:methods*; D000775:Anesthesia, Spinal; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D018014:Gene Transfer Techniques; D006564:Herpesviridae / Q000235:genetics; D008139:Loperamide / Q000494:pharmacology*; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D018076:DNA, Complementary; D017450:Receptors, Opioid, mu; D008139:Loperamide