Studies on the antinociceptive effect of [Nphe1]nociceptin(1-13)NH2 in mice

Neurosci Lett. 2001 Dec 4;316(1):25-8. doi: 10.1016/s0304-3940(01)02352-7.


Nociceptin/orphanin FQ (NC) and its receptor (OP(4)) have been implicated in the regulation of various functions including nociception. [Nphe(1)]NC(1-13)NH(2) (Nphe) is a selective OP(4) antagonist which prevents the pronociceptive effects of supraspinal NC and causes per se a naloxone-insensitive antinociceptive effect. In the present study, we tested Nphe in wild type (WT) and OP(4) receptor knock out mice and found that a clear antinociceptive effect of the antagonist was evident only in WT mice. Moreover, we evaluated, over 5 days of treatment, the antinociceptive effects of Nphe in comparison with those of DAMGO and found that tolerance develops to the effects of the opioid receptor agonist but not to Nphe. These data demonstrate that the antinociceptive action of Nphe is due to the block of OP(4) receptors and that no tolerance develops to this kind of antinociception.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacology*
  • Analgesics, Opioid / administration & dosage
  • Animals
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / administration & dosage
  • In Vitro Techniques
  • Injections, Intraventricular
  • Isometric Contraction / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Narcotic Antagonists*
  • Opioid Peptides / administration & dosage
  • Opioid Peptides / pharmacology*
  • Pain Measurement / drug effects
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Reaction Time / drug effects
  • Receptors, Opioid / deficiency


  • Analgesics
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • nociceptin-(1-13)-NH2, NPhe(1)-
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • nociceptin receptor