Peripheral Deltorphin II Inhibits Nociceptors Following Nerve Injury
Autor: | Petr Dubový, Marek Joukal, Lucy Vulchanova, Christopher N. Honda, Cecilia Huffman |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
spared nerve injury deltorphin II Pharmacology delta opioid receptors δ-opioid receptor 03 medical and health sciences 0302 clinical medicine Naltrindole medicine Pharmacology (medical) Tibial nerve Original Research neuropathic pain business.industry lcsh:RM1-950 Nerve injury 030104 developmental biology nociceptors lcsh:Therapeutics. Pharmacology Opioid 030220 oncology & carcinogenesis Hyperalgesia Neuropathic pain Nociceptor medicine.symptom business medicine.drug |
Zdroj: | Frontiers in Pharmacology, Vol 11 (2020) Frontiers in Pharmacology |
ISSN: | 1663-9812 |
Popis: | 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 naive 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 naive 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. |
Databáze: | OpenAIRE |
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