Lack of the nociceptin receptor does not affect acute or chronic nociception in mice.
The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor ORL-1, also designated opioid receptor 4 (OP(4)) are involved in the modulation of nociception. Using OP(4)-knockout mice, we have studied their response following opioid receptor stimulation and under neuropathic conditions.In vas deferens from wild-type and OP(4)-knockout mice, DAMGO (mu/OP(3) agonist), deltorphine II (delta/OP(1) agonist) and (-)-U-50488 (kappa/OP(2) agonist) induced similar concentration-dependent inhibition of electrically-evoked contractions. Naloxone and naltrindole (delta/OP(1) antagonists) shifted the curves of DAMGO (pA(2)=8.6) and deltorphine II (pA(2)=10.2) to the right, in each group. In the hot-plate assay, N/OFQ (10 nmol per mouse, i.t.) increased baseline latencies two-fold in wild-type mice while morphine (10mg/kg, s.c.), deltorphine II (10 nmol per mouse, i.c.v.) and dynorphin A (20 nmol per mouse, i.c.v.) increased hot-plate latencies by about four- to five-fold with no difference observed between wild-type and knockout mice. Furthermore, no change was evident in the development of the neuropathic condition due to chronic constriction injury (CCI) of the sciatic nerve, after both thermal and mechanical stimulation. Altogether these results suggest that the presence of OP(4) receptor is not crucial for (1) the development of either acute or neuropathic nociceptive responses, and for (2) the regulation of full receptor-mediated responses to opioid agonists, even though compensatory mechanisms could not be excluded.
Bertorelli
Rosalia
R
Schering-Plough Research Institute, San Raffaele Science Park, Via Olgettina 58, Milan, Italy. rosalia.bertorelli@spcorp.com
Bastia
Elena
E
Citterio
Francesca
F
Corradini
Laura
L
Forlani
Angelo
A
Ongini
Ennio
E
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011957:Receptors, Opioid / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004399:Dynorphins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D009270:Naloxone; D009271:Naltrexone; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C059567:deltorphin; C051844:norbinaltorphimine; C055382:naltrindole; C000722287:Oprl1 protein, mouse