The Analgesic Effect and Mechanism of Action of Processed Aconiti Tuber and Its Alkaloid

Abstract

A processed Aconiti tuber, Tsumura-shuchi-bushi-matsu (TJ-3021), has potent antinociceptive activity in hyperalgesia induced by repeated cold stress (RCS) in rats. The present study was undertaken to study the analgesic effects and mechanism of action of TJ-3021 on the descending inhibitory system, in particular the α2-adrenergic, serotonergic, and opioid systems in rats. The nociceptive threshold determined by pressure decreased in rats exposed to RCS, but it increased markedly after oral administration of TJ-3012. Intrathecal and intraperitoneal administration of the selective α2-adrenoceptor antagonists, idazoxan (IDA), and methysergide (METH), a 5-hydroxytrypta-mine receptor antagonist, significantly reduced the analgesic effect of TJ-3021 in RCS rats. Intraperitoneal administration of the opioid receptor antagonist naloxone had no effect. Both oral and intracisternal administration of mes-aconitine (MA), one of the main potent aconitine alkaloids in TJ-3021, produced remarkable analgesia in non-RCS rats. These effects were reduced significantly by intraperitoneal administration of either IDA or METH. However, intrathecal administration of MA did not induce any significant increase in the nociceptive threshold. These results suggest that the analgesic effect of TJ-3021 depends partly on the actions of MA on the brainstem, but not on the spinal cord. We postulate that the effect is mediated by both α2-adrenergic and serotonergic systems. It appears that further study on the opioid receptors will be necessary.