Enhanced Peripheral Analgesia Using Virally Mediated Gene Transfer of the μ-Opioid Receptor in Mice

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 enhanc...

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Published in:	Anesthesiology (Philadelphia) Vol. 108; no. 2; pp. 305 - 313
Main Authors:	GUOHUA ZHANG, MOHAMMAD, Husam, PEPER, Brad D, RAJA, Srinivasa, WILSON, Steven P, SWEITZER, Sarah M
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott 01-02-2008
Subjects:	Analgesia - methods Anesthesia Anesthesia, Spinal Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences DNA, Complementary - genetics Ganglia, Spinal - drug effects Ganglia, Spinal - physiology Gene Transfer Techniques Herpesviridae - genetics Loperamide - pharmacology Medical sciences Mice Nerve Endings - drug effects Nerve Endings - physiology Receptors, Opioid, mu - genetics Skin - innervation Spinal Cord - drug effects Spinal Cord - physiology Analgesia Vertebrata Mammalia Mouse Animal Rodentia Anesthesia
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0003-3022 1528-1175
DOI:	10.1097/01.anes.0000299836.61785.79