Site of analgesic action of aconitine and the relation between its action and the central noradrenergic system

After sc administration, the analgesic action of Ac was found to be dose-dependent, and icv administration of Ac induced a more potent analgesic action. However, spinal intrathecal injections of the same amounts of Ac had no analgesic action. These results suggest that the analgesic action of Ac is central in origin and that it acts mainly on supraspinal substrate. The analgesic action of Ac at 65 yg/kg was abolished or significantly reduced by ip reserpine, diethyldithiocarbamate and phenoxybenzamine. No effect was seen on the analgesic action of Ac after ip propranolol or phentolamine administration. Norepinephrine icv apparently strengthened the analgesic action of Ac, while icv naloxone or phenoxybenzamine remarkably decreased the Ac-induced analgesia. But no effects were seen on the analgesic action of Ac after spinal intrathecal injection of phenoxybenzamine. The analgesic action of Ac was abolished after bilateral destruction of the nucleus, ie, the locus coeruleus, where the cell bodies of the central noradrenergic neurons lie, by an electrolytic lesion method. These results suggest that the analgesic action of Ac may be associated with the central noradrenergic system (probably indirectly by acting on a receptors rather than on (3 receptors) and opioid pathway.