Endogenous nociceptin signaling and stress-induced analgesia

Neuroreport. 2001 Oct 8;12(14):3009-13. doi: 10.1097/00001756-200110080-00006.

Abstract

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims). High severity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that was partially antagonized by naloxone, completely blocked by NC and potentiated by [Nphe1]NC(-13)NH2. These findings confirm the anti-analgesic role of supraspinal NC and suggest that endogenous NC signaling counteracts the opioid component of SIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia*
  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Male
  • Mice
  • Narcotic Antagonists
  • Opioid Peptides / antagonists & inhibitors
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacology
  • Pain / metabolism*
  • Pain / physiopathology
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peptide Fragments / pharmacology
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Opioid / metabolism*
  • Signal Transduction / physiology*
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology
  • Swimming / physiology

Substances

  • Narcotic Antagonists
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-
  • nociceptin
  • nociceptin receptor