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

Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10949-53. doi: 10.1073/pnas.95.18.10949.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Calcium / metabolism
  • GTP-Binding Proteins / metabolism
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Ion Transport
  • Mice
  • Mutation
  • Nerve Endings / drug effects*
  • Nerve Endings / metabolism
  • Nociceptin
  • Oligonucleotides, Antisense
  • Opioid Peptides / pharmacology*
  • Pertussis Toxin
  • Receptors, Opioid / agonists
  • Substance P / metabolism*
  • Tachykinins / genetics
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Oligonucleotides, Antisense
  • Opioid Peptides
  • Receptors, Opioid
  • Tachykinins
  • Virulence Factors, Bordetella
  • Substance P
  • Inositol 1,4,5-Trisphosphate
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Calcium