Studies on the antinociceptive effect of [Nphe1]nociceptin(1-13)NH2 in mice.
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.
Di Giannuario
A
A
Laboratorio di Farmacologia, Istituto Superiore di Sanita', 00161 Rome, Italy.
Rizzi
A
A
Pieretti
S
S
Guerrini
R
R
Bertorelli
R
R
Salvadori
S
S
Regoli
D
D
Calo
G
G
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007537:Isometric Contraction / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000172:deficiency; D000094942:Nociceptin Receptor
D000700:Analgesics; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse