Pain Medicine  |   May 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 2017 Frontiers in Opioid Pharmacotherapy Symposium article.
    This is a 2017 Frontiers in Opioid Pharmacotherapy Symposium 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.
    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.×
  • 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 / Basic Science / Infectious Disease / Pain Medicine / Opioid
Pain Medicine   |   May 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 5 2018, Vol.128, 967-983. doi:10.1097/ALN.0000000000002063
Anesthesiology 5 2018, Vol.128, 967-983. 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.