Peripheral Deltorphin II Inhibits Nociceptors Following Nerve Injury

Marek Joukal, Lucy Vulchanova, Cecilia Huffman, Petr Dubový, Christopher N Honda

Research output: Contribution to journalArticlepeer-review

Abstract

Clinical and preclinical studies have revealed that local administration of opioid agonists into peripheral tissue attenuates inflammatory pain. However, few studies have examined whether peripherally restricted opioids are effective in reducing mechanical allodynia and hyperalgesia that usually follows nerve injury. The aim of the present study was to determine whether the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic pain conditions is depressed by direct activation of delta opioid receptors (DORs) on their peripheral terminals. A murine model of peripheral neuropathic pain was induced with a spared nerve (tibial) injury, in which mice survived 7 or 28 days after surgery before electrophysiological testing began. Control groups comprised naïve and sham-operated animals. An ex vivo preparation of mouse plantar skin with attached tibial nerve was used to examine electrophysiologically the effects of the selective DOR agonist, deltorphin II, on the response properties of individual cutaneous C-fiber nociceptors. In contrast to naïve and sham-operated animals, deltorphin II induced an inhibition of the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic conditions. The effects of deltorphin II were concentration-dependent and prevented by pretreatment with naltrindole indicating DOR-mediated inhibitory effects of deltorphin II. Our results provide the first direct evidence for expression of functional DORs on mechanical nociceptors innervating skin in an animal model of neuropathic pain.

Original languageEnglish (US)
Article number1151
JournalFrontiers in Pharmacology
Volume11
DOIs
StatePublished - Jul 31 2020

Bibliographical note

Funding Information:
This work was supported by PHS grants DA09641 (CNH), DE021996 (LV), NS088518 (LV), Proshek-Fulbright Scholarship (MJ) and funds from the Faculty of Medicine,

Keywords

  • delta opioid receptors
  • deltorphin II
  • neuropathic pain
  • nociceptors
  • spared nerve injury

PubMed: MeSH publication types

  • Journal Article

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