Nociceptin/orphanin FQ-induced nociceptive responses through substance P release from peripheral nerve endings in mice

Makoto Inoue, Motomasa Kobayashi, Shunji Kozaki, Andreas Zimmer, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

Abstract

We have studied the in vivo signaling mechanisms involved in nociceptin/orphanin FQ (Noci)-induced pain responses by using a flexor- reflex paradigm. Noci was 10,000 times more potent than substance P (SP) in eliciting flexor responses after intraplantar injection into the hind limb of mice, but the action of Noci seems to be mediated by SP. Mice pretreated with an NK1 tachykinin receptor antagonist or capsaicin, or mice with a targeted disruption of the tachykinin 1 gene no longer respond to Noci. The action of Noci appears to be mediated by the Noci receptor, a pertussis toxin-sensitive G protein-coupled receptor that stimulates inositol trisphosphate receptor and Ca2+ influx. These findings suggest that Noci indirectly stimulates nerve endings of nociceptive primary afferent neurons through a local SP release.

Original languageEnglish (US)
Pages (from-to)10949-10953
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number18
DOIs
StatePublished - Sep 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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