Selective inhibition of responses of feline dorsal horn neurones to noxious cutaneous stimuli by tizanidine (DS103-282) and noradrenaline: involvement of alpha 2-adrenoceptors

The effects of tizanidine (DS103-282) were compared with those of noradrenaline and other adrenoceptor agonists on responses of laminae IV and V neurones in the lumbar dorsal horn to noxious and innocuous cutaneous stimuli in the anaesthetized cat. Tizanidine, noradrenaline and the alpha 2-receptor agonist, clonidine, depressed spontaneous activity and responses to noxious, but not those to innocuous, stimuli when administered iontophoretically, either near the recording site in laminae IV-V, or into laminae II-III, i.e. 300-900 microns dorsal to the recording site. Iontophoretic ejection of dopamine, the beta-agonist isoprenaline and the alpha 1-agonists phenylephrine and amidephrine had no effect at either site, or only relatively weak and sometimes non-selective depressant actions on neuronal responses to cutaneous stimuli. The preferential depressant actions of tizanidine, noradrenaline and clonidine were antagonized by the selective alpha 2-antagonist RX781094 administered iontophoretically at the same site as the agonists, and by intravenously administered yohimbine. In contrast, the alpha 1-antagonists, prazosin and WB4101, the beta-antagonist, sotalol and opiate antagonist, naloxone did not alter the depressant actions of these agonists on laminae IV and V neurones. These findings indicate that the selective inhibitory effect of tizanidine and noradrenaline on responses of laminae IV and V neurones to noxious peripheral stimuli are mediated at alpha 2-adrenoceptors situated in either laminae IV and V or laminae II-III. The possible physiological relevance of these receptors is discussed.