Abstract
The study was carried out to provide further evidence that the two pyrazolone derivatives, metamizol and aminophenazone, produce central antinociceptive effects by stimulating inhibition descending from the periaqueductal grey (PAG) to the spinal cord. Experiments were carried out on rats in which the tail-flick response to radiant heat, nociceptive activity in ascending axons of the spinal cord, and activity of neurones in the PAG and the substantia nigra were studied. Microinjection of procaine (10 micrograms) into the PAG reduced the tail-flick latency and abolished the increase in latency caused by i.p. injection of metamizol (40 mg/kg) and aminophenazone (150 mg/kg); it did not significantly reduce the antinociceptive effect of i.p. injection of morphine (2 mg/kg). Threshold doses of morphine (1 and 2 micrograms) administered by intrathecal (i.t.) injection potentiated the effect of threshold doses of metamizol injected i.p. (10 mg/kg) or into the PAG (10 micrograms) in the tail-flick test. Morphine (2 micrograms) injected i.t. potentiated the effect of i.v. injection of metamizol (80 mg/kg) on nociceptive activity in ascending axons by eliminating the stimulant effect of metamizol on about one third of the axons. Threshold doses of morphine injected i.t. failed to potentiate the antinociceptive effect of aminophenazone (50 mg/kg) injected i.p. in the tail-flick test. The results support the view that metamizol and aminophenazone activate pathways descending from the PAG and exerting an inhibitory effect on nociceptive impulse transmission at the spinal level.
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