• Amanda H Klein, Husam K Mohammad, Rabiah Ali, Brad Peper, Steven P Wilson, Srinivasa N Raja, Matthias Ringkamp, and Sarah Sweitzer.
• From the Departments of Neurosurgery (A.H.K., M.R.) and Anesthesiology and Critical Care Medicine (S.R.), Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Pharmacology, Physiology, Neuroscience, School of Medicine, University of South Carolina, Columbia, South Carolina (H.K.M., R.A., B.P., S.P.W., S.S.). Current positions: Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, Minnesota (A.H.K.); and College of Health and Human Services, Concordia University, Portland, Oregon (S.S.).
• Anesthesiology. 2018 May 1; 128 (5): 967-983.

BackgroundThe current study used recombinant herpes simplex virus type I to increase expression of µ-opiate receptors and the opioid ligand preproenkephalin in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted that viral vector delivery of a combination of genes encoding the µ-opioid receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid analgesia. The behavioral effects would be paralleled by changes in response properties of primary afferent neurons.MethodsRecombinant herpes simplex virus type 1 containing cDNA sequences of the µ-opioid receptor, human preproenkephalin, a combination, or Escherichia coli lacZ gene marker (as a control) was used to investigate the role of peripheral opioids in neuropathic pain behaviors.ResultsInoculation with the µ-opioid receptor viral vector (n = 13) reversed mechanical allodynia and thermal hyperalgesia and produced leftward shifts in loperamide (ED50 = 0.6 ± 0.2 mg/kg vs. ED50 = 0.9 ± 0.2 mg/kg for control group, n = 8, means ± SD) and morphine dose-response curves (ED50 = 0.3 ± 0.5 mg/kg vs. ED50 = 1.1 ± 0.1 mg/kg for control group). In µ-opioid receptor viral vector inoculated C-fibers, heat-evoked responses (n = 12) and ongoing spontaneous activity (n = 18) were decreased after morphine application. Inoculation with both µ-opioid receptor and preproenkephalin viral vectors did not alter mechanical and thermal responses.ConclusionsIncreasing primary afferent expression of opioid receptors can decrease neuropathic pain-associated behaviors and increase systemic opioid analgesia through inhibition of peripheral afferent fiber activity.

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