Intrathecal administration of thiorphan and bestatin enhances the antinociception and release of Met-enkephalin induced by beta-endorphin intraventricularly in anesthetized rats.

Effects of bestatin and thiorphan administered intrathecally, on inhibition of the tail-flick response and the release of Met-enkephalin induced by beta-endorphin administered intraventricularly were studied in anesthetized rats. Intrathecal pretreatment with 100 micrograms of thiorphan or bestatin potentiated the inhibition of the tail-flick response induced by beta-endorphin injected intraventricularly in pentobarbital anesthetized rats; the ED50 values for beta-endorphin were decreased 5- and 7-fold by thiorphan and bestatin, respectively. To determine if the potentiating effect was due to the inhibition of the degradation of Met-enkephalin released by intraventricular beta-endorphin, the effects of intrathecal perfusion with thiorphan or bestatin on the release of immunoreactive Met-enkephalin from the spinal cord by intraventricular injection of beta-endorphin were studied. beta-Endorphin injected into the 4th ventricle at a dose of 5 micrograms increased immunoreactive Met-enkephalin in the spinal perfusate in urethane-anesthetized rats. Thiorphan or bestatin (1 x 10(-7) to 1 x 10(-4) M each) increased the amount of immunoreactive Met-enkephalin released by intraventricular beta-endorphin in a dose-dependent manner. The results provide additional evidence for the hypothesis that antinociception induced by beta-endorphin is mediated by release of Met-enkephalin.