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 (OP4) are involved in the modulation of nociception. Using OP4-knockout mice, we have studied their response following opioid receptor stimulation and under neuropathic conditions. In vas deferens from wild-type and OP4-knockout mice, DAMGO ( mu/OP3 agonist), deltorphine II (delta/OP1 agonist) and (-)-U-50488 (kappa/OP2 agonist) induced similar concentration-dependent inhibition of electrically-evoked contractions. Naloxone and naltrindole (delta/OP1 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 (10 mg/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 OP4 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. Published by Elsevier Science Inc.