Mu receptor and Gi2alpha antisense attenuate [D-Met2]-FMRFamide antinociception in mice.

FMRFamide (Phe-Met-Arg-Phe-NH2) and several analogs produce centrally-mediated, naloxone-reversible antinociception, but have minimal affinity for opioid receptor (sub)types. In the present study, the antinociception in mice (55 degrees C tail-flick test) produced by supraspinal (intracerebroventricular; i.c.v.) administration of [D-Met2]-FMRFamide (a stable analog of FMRFamide) was attenuated by pretreatment with i.c.v. oligodeoxyribonucleotide antisense to the opioid mu receptor or by antisense to the Gi2alpha G-protein subunit. These data suggest that [D-Met2]-FMRFamide produces its antinociception via an opioid interneuron.