Antiallodynic effects of a CCK(B) antagonist in rats with nerve ligation injury: Role of endogenous enkephalins

Michael L. Nichols, Di Bian, Michael H. Ossipov, T. Philip Malan, Frank Porreca

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Cholecystokinin (CCK) may act as an endogenous anti-opioid and blockade of CCK receptors can enhance the potency and efficacy of morphine. This effect is blocked by opioid delta (δ) receptor antagonists, suggesting a tonic inhibitory action of CCK to diminish the release and/or availability of endogenous enkephalins. The present studies have further evaluated this possibility by studying the antiallodynic actions of a CCK(B) antagonist (L365,260) alone, or in the presence of thiorphan (a neutral endopeptidase inhibitor) in a model of peripheral neuropathy. Animals subjected to nerve injury, but not sham controls, exhibited long lasting, stable mechanical anodynia. Intrathecal (i.t.) administration of L365,260 or thiorphan alone did not alter allodynia. However, co-administration of these compounds produced a significant antiallodynic action which was antagonized by receptor selective doses of naltrindole, an opioid δ receptor antagonist. In addition, antisera to [Leu5]enkephalin, but not to [Met5]enkephalin, also blocked the antiallodynic action of thiorphan plus L365,260. These data suggest that blockade of CCK(B) receptors may enhance the actions or availability of endogenous [Leu5]enkephalin or a like substance which can elicit a significant antiallodynic action via opioid δ receptors when its degradation is by inhibited by thiorphan. The data suggest that δ opioids are involved in regulation of some aspects of nerve-injury induced pain.

Original languageEnglish (US)
Pages (from-to)161-164
Number of pages4
JournalNeuroscience Letters
Volume215
Issue number3
DOIs
StatePublished - Sep 13 1996

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Keywords

  • Allodynia
  • Antisera
  • Cholecystokinin
  • Na ltrindole
  • Nerve injury
  • Neuropathic pain
  • Thiorphan
  • [Leu]enkephalin

ASJC Scopus subject areas

  • Neuroscience(all)

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