INTRATHECAL ADMINISTRATION OF P-HYDROXYMERCURIBENZOATE OR PHOSPHORAMIDON BESTATIN-COMBINED INDUCES ANTINOCICEPTIVE EFFECTS THROUGH DIFFERENT OPIOID MECHANISMS/

The antinociceptive effect of intrathecally (i.t.) administered protea se inhibitors was tested against capsaicin (800 ng) injected into the dorsal surface of a hindpaw. Both p-hydroxymercuribenzoate (2-8 nmol), a cysteine protease inhibitor, and phosphoramidon (1-4 nmol), an endo peptidase 24.11 inhibitor in the presence of bestatin (0.25 nmol) an a minopeptidase inhibitor, administered i.t. 60 min prior to the injecti on of capsaicin produced a dose-dependent reduction of the capsaicin-i nduced paw licking and biting response. p-Hydroxymercuribenzoate (4 nm ol)-induced antinociception was significantly antagonized by nor-binal torphimine, a selective kappa-opioid receptor antagonist, but not by n altrindole, a selective delta-opioid receptor antagonist. On the other hand, phosphoramidon (4 nmol) /bestatin-induced antinociception was s ignificantly antagonized by naltrindole, but not by nor-binaltorphimin e. The results indicate that the antinociceptive effect of p-hydroxyme rcuribenzoate may be due to the inhibition of a cysteine protease degr ading endogenous dynorphins whereas phosphoramidon in the presence of bestatin blocks the degradation of enkephalins.