Strain-dependent effects of supraspinal orphanin FQ/nociceptin on thermal nociceptive sensitivity in mice

Despite much study since its discovery in 1995, the effects of orphanin FQ/ nociceptin (OFQ/N), the endogenous ligand of the 'orphan' opioid receptor, on nociceptive sensitivity remain unclear. Different laboratories have vari ously reported hyperalgesic, analgesic, anti-analgesic or no effect of the peptide on thermal assays following supraspinal injection in rodents. We an d others have argued previously that methodological inconsistencies and exp erimental parameters may explain some of the contradictions in the literatu re, especially in mice where intracerebroventricular (i.c.v.) injections pr oceed directly through the skull. We report presently that both the magnitu de of stress-induced analgesia (SIA) produced by such i.c.v. injections, an d the ability of OFQ/N to antagonize this opioid-mediated SIA, are strain-d ependent. Specifically, significant injection-related SIA was observed in f our of six strains studied (outbred: CD-I, SW; inbred: AKR/J, BALB/cJ, C3H/ HeJ, CBA/J) on the 47.5 degrees C tail-withdrawal assay, and OFQ/N blocked this SIA in two strains. These data suggest that genetic variability among subject populations may underlie the inconsistent findings among researcher s, and may in addition provide a promising avenue for future study of this novel neuromodulator, (C) 1999 Elsevier Science Ireland Ltd. All rights res erved.