Mechanism of the antinociceptive action of mesaconitine: participation of brain stem and lumbar enlargement.

The antinociceptive action of mesaconitine (MA) microinjected into the nucleus reticularis gigantocellularis (NRGC), the nucleus reticularis paragigantocellularis (NRPG), the periaqueductal gray (PAG) or the lumbar enlargement was investigated in rats by use of the tail immersion test. In addition, the effects of beta-adrenoceptor antagonists and an alpha-adrenoceptor antagonist administered intrathecally (i.t.) on the antinociceptive action of MA given into the NRPG were also examined by the tail immersion test. MA (50, 100 ng per rat) microinjected into the NRGC, the NRPG, and PAG and the lumbar enlargement increased the response latency in rats in a dose-dependent fashion. MA (50 ng per rat) microinjected into neighbouring sites, the nucleus reticularis parvocellularis, the nucleus originis nervi abducentis and the fasciculus longitudinalis medialis, elicited no significant effect. Intrathecally administered propranolol (1 and 5 micrograms per rat), atenolol (1 and 5 micrograms per rat) and IPS-339 (1 and 5 micrograms per rat) remarkably inhibited the increase of the response latency induced by MA (50 ng per rat) given into the NRPG. Intrathecally administered phenoxybenzamine (1 and 5 micrograms per rat) inhibited the increase of the response latency induced by MA (50 ng per rat) injected into the NRPG but to a lesser extent than the beta-adrenoceptor antagonists. It is concluded that the NRGC, the NRPG, the PAG and the lumbar enlargement are involved in the sites of the antinociceptive action of MA and that the antinociceptive effect of MA administered into NRPG is elicited by activation of the inhibitory noradrenergic neurones from the NRPG in particularly via beta-receptor-mediated effects of noradrenaline.