Brainstem sites differentially sensitive to beta-endorphin and morphine for analgesia and release of met-enkephalin in anesthetized rats

Abstract

Mapping of the brainstem regions sensitive to beta-endorphin and morphine for antinociception and Met-enkephalin release was performed in rats. Antinociception was assessed by the tail-flick test in pentobarbital-anesthetized rats and the release of immunoreactive Met-enkephalin from the spinal cord was measured by lumbar-cisternal perfusion in urethane-anesthetized rats. The sites in the brainstem most sensitive to beta-endorphin (2 micrograms) for inhibition of the tail-flick response and Met-enkephalin release were located in areas in the caudal medial medulla such as raphe obsacurus nucleus and raphe pallidus nucleus and the adjacent midline reticular formation. Sites in the rostral medial medulla were less sensitive to beta-endorphin for both antinociception and release of Met-enkephalin. The regions 1 mm and more lateral to the midline were not sensitive to beta-endorphin. The sites sensitive to morphine sulfate (4 micrograms) for antinociception were located in areas in the rostral ventromedial medulla such as raphe magnus nucleus, gigantocellular reticular nucleus and gigantocellular reticular nucleus alpha. Raphe obscurus nucleus, which was sensitive to beta-endorphin, was not sensitive to morphine for antinociception. Locus coeruleus was sensitive to morphine and beta-endorphin for antinociception. No sites sensitive to morphine were found for Met-enkephalin release. The correlation between the brainstem sites sensitive to beta-endorphin for the production of antinociception and the release of Met-enkephalin suggests that the antinociception induced by beta-endorphin is mediated by the release of Met-enkephalin. The findings of different brainstem sites sensitive to beta-endorphin and morphine support the hypothesis of different modes of pharmacological actions for beta-endorphin and morphine.