Newly Published
Pain Medicine  |   January 2018
Overexpression of µ-Opioid Receptors in Peripheral Afferents, but Not in Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances Opioid Analgesia in Mouse
Author Notes
  • 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.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • This is a Frontiers in Opioid Pharmacotherapy article. Part of the work presented in this article has been presented as a poster at the Society for Neuroscience 38th Annual Meeting, 774.12, Washington, D.C., USA, November 15–19, 2008.
    This is a Frontiers in Opioid Pharmacotherapy article. Part of the work presented in this article has been presented as a poster at the Society for Neuroscience 38th Annual Meeting, 774.12, Washington, D.C., USA, November 15–19, 2008.×
  • Submitted for publication June, 14, 2017. Accepted for publication November 28, 2017.
    Submitted for publication June, 14, 2017. Accepted for publication November 28, 2017.×
  • Acknowledgments: The authors thank Claire Levine, M.S., E.L.S. (Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland), for her editorial help.
    Acknowledgments: The authors thank Claire Levine, M.S., E.L.S. (Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland), for her editorial help.×
  • Research Support: Supported by U.S. National Institutes of Neurological Disease and Stroke grant No. NS-26363 (to Dr. Raja), by the University of South Carolina Department of Pharmacology, Physiology, Neuroscience (to Drs. Sweitzer and Wilson), and by National Institutes of Health F32 fellowship grant No. DA-036991 (to Dr. Klein).
    Research Support: Supported by U.S. National Institutes of Neurological Disease and Stroke grant No. NS-26363 (to Dr. Raja), by the University of South Carolina Department of Pharmacology, Physiology, Neuroscience (to Drs. Sweitzer and Wilson), and by National Institutes of Health F32 fellowship grant No. DA-036991 (to Dr. Klein).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Klein: University of Minnesota, College of Pharmacy, Duluth, Minnesota 55812. ahklein@d.umn.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Pain Medicine
Pain Medicine   |   January 2018
Overexpression of µ-Opioid Receptors in Peripheral Afferents, but Not in Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances Opioid Analgesia in Mouse
Anesthesiology Newly Published on January 16, 2018. doi:10.1097/ALN.0000000000002063
Anesthesiology Newly Published on January 16, 2018. doi:10.1097/ALN.0000000000002063
Abstract

Background: The 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.

Methods: Recombinant 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.

Results: Inoculation 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.

Conclusions: Increasing primary afferent expression of opioid receptors can decrease neuropathic pain-associated behaviors and increase systemic opioid analgesia through inhibition of peripheral afferent fiber activity.