Pertussis toxin inhibits antinociception produced by intrathecal injection of morphine, noradrenaline and baclofen

Abstract

The effect of intrathecal pretreatment with pertussis toxin on the spinal antinociceptive effect of morphine, noradrenaline and L-baclofen was examined in rats implanted with chronic indwelling cannulas. Pretreatment with 0.25-0.75 μg pertussis toxin for 2-7 days inhibited antinociception produced by intrathecal injection of all three agents in the tail flick test. Inhibition also occurred in the hot plate test, butwas less pronounced than in the tail flick test. When doses of the three agents giving similar levels of antinociception were compared in a single group, the degree of inhibition of antinociception was comparable. Inhibition of the effect of noradrenaline was observed up to 14 days following pretreatment. The sensitivity of spinal antinociception to pertussis toxin suggests involvement of a guanine nucleotide regulatory protein in spinal actions of morphine, noradrenaline and L-baclofen. There is support in the literature for the additional involvement of adenylate cyclase in the action of morphine and noradrenaline but not of baclofen. © 1988.