Effects of tizanidine (DS 103–282) on dorsal horn convergent neurones in the rat

It is concluded that tizanidine depresses specifically the activities of dorsal horn convergent neurones, probably in part by a post-synaptic inhibitory action, which could explain, at least partially, the analgesic action of this compound.

Abstract

The effects of tizanidine, a new muscle relaxant, 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiazole (DS 103-282) were studied on the activity of lumbar dorsal horn convergent neurons in anaesthetized paralysed rats. Following i.v. administration of tizanidine both the A- and C-fibre evoked responses were depressed in a dose-dependent manner in the 0.125-1.0 mg/kg range. The smaller dose employed (0.125 mg/kg) induced a significant depression of the C-fibre evoked responses (39.6 +/- 13.4% of the control responses) and a total recovery was observed 10 min after the injection: when the doses were increased, stronger and longer-lasting depressant effects were obtained. Identical but less powerful effects were observed on A-fibre responses. None of the depressive effects was correlated with variations in blood pressure. Microelectrophoretically applied tizanidine was found to depress current-dependently, the discharges of convergent neurones evoked by microelectrophoretically applied DL-homocysteic acid. In contrast, tizanidine (0.5, 1 mg/kg; i.v.) was found to be ineffective against the activities of non-nociceptive neurones triggered by mechanical stimulation of their receptive fields. It is concluded that tizanidine depresses specifically the activities of dorsal horn convergent neurones, probably in part by a post-synaptic inhibitory action. Owing to the role of convergent neurones in pain processes, the present result could explain, at least partially, the analgesic action of this compound.