Differential antinociceptive effects of sendide, a NK sub(1)-receptor antagonist, and morphine in the capsaicin test

The peptide NK sub(1)-receptor antagonists, sendide and [D-Trp super(7)]sendide, have been evaluated for antinociceptive activity in the capsaicin test. Both peptides, injected intrathecally (i.t.) 5 min prior to intraplantar capsaicin, produced a dose-dependent reduction of the capsaicin-induced paw licking response. Naloxone pretreatment did not affect sendide- and [D-Trp super(7)]sendide-induced antinociception, wherease naloxone at a dose of 0.5 mg/kg antagonized the antinociceptive effect of i.t. administered morphine. Conversely, the antinociceptive action induced by both NK sub(1)-receptor antagonists was reduced significantly by i.t. co-administration of substance P. Morphine-induced antinociception was not antagonized by co-administration of substance P. The results led us to the understanding of differential action mechanism of NK sub(1)-receptor antagonist- and morphine-induced antinociception as assayed by the capsaicin test.