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

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in the regulation of various functions including nociception. [Nphe(1)]NC(1-13 )NH2 (Nphe) is a selective OP4 antagonist which prevents the pronociceptive effects of supraspinal NC and causes per se a naloxone-insensitive antinoc iceptive effect. In the present study, we tested Nphe in wild type (WT) and OP4 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 wit h those of DAMGO and found that tolerance develops to the effects of the op ioid receptor agonist but not to Nphe. These data demonstrate that the anti nociceptive action of Nphe is due to the block of OP4 receptors and that no tolerance develops to this kind of anti nociception. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.