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

Abstract

Effects of bestatin and thiorphan administered intrathecally, on inhibition of the tail-flick response and the release of Met-enkephalin induced by β-endorphin administered intraventricularly were studied in anesthetized rats. Intrathecal pretreatment with 100 μg of thiorphan or bestatin potentiated the inhibition of the tail-flick response induced by β-endorphin injected intraventricularly in pentobarbital anesthetized rats; the ED50 values for β-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 β-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 β-endorphin were studied. β-Endorphin injected into the 4th ventricle at a dose of 5 μg increased immunoreactive Met-enkephalin in the spinal perfusate in urethane-anesthetized rats. Thiorphan or bestatin (1 × 10 −7 to 1 × 10 −4M each) increased the amount of immunoreactive Met-enkephalin released by intraventricular β-endorphin in a dose-dependent manner. The results provede additional evidence for the hypothesis that antinociception induced by β-endorphin is mediated by release of Met-enkephalin.