Overexpression of μ-opioid receptors in peripheral afferents, but not in combination with enkephalin, decreases neuropathic pain behavior and enhances opioid analgesia in mouse

Amanda H. Klein, Husam K. Mohammad, Rabiah Ali, Brad Peper, Steven P. Wilson, Srinivasa N. Raja, Matthias Ringkamp, Sarah Sweitzer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)967-983
Number of pages17
JournalAnesthesiology
Volume128
Issue number5
DOIs
StatePublished - Jan 1 2018

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ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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