THE ANTINOCICEPTIVE ACTION OF AN ALPHA(2)-ADRENOCEPTOR AGONIST IN THE SPINAL DORSAL HORN IS DUE TO A DIRECT SPINAL ACTION AND NOT TO ACTIVATION OF DESCENDING INHIBITION

In this electrophysiological study we tried to find out whether the spinal antinociceptive effect of a supraspinally administered alpha(2)-adrenoceptor agonist is due to a direct spinal effect or to activation of descending inhibition. The responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were studied following application of medetomidine, a selective alpha(2)-adrenergic agonist, into the rostroventromedial medulla (RVM) or directly onto the spinal cord of the intact and in spinal rats. The noxious electrical stimuli were applied to the ipsilateral receptive field in the plantar region of the hind paw, and responses mediated by A- and C-fibers to WDR neurons were separately evaluated. The reversal of medetomidine-induced effects was attempted by a systemic administration of atipamezole, a selective alpha(2)-adrenoceptor antagonist. Medetomidine injection into the RVM produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses to WDR neurons of the spinal dorsal horn in both intact and spinal rats. Paradoxically, the spinal antinociceptive effect of supraspinally administered medetomidine was stronger in spinal rats. The A-fiber-mediated responses were significantly less attenuated by medetomidine than the C-fiber-mediated responses to the WDR neurons. Also a direct application of medetomidine onto the spinal cord produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses, and this effect was identical in intact and in spinal rats. The medetomidine doses producing spinal antinociception were considerably lower with a direct spinal application than with a supraspinal application. These results indicate that spinal antinociception following spinal or supraspinal application of an alpha(2)-adrenergic agonist is due to a direct activation of spinal alpha(2)-adrenoceptors and not to descending inhibition. Activation of supraspinal alpha(2)-adrenoceptors counteracts the spinal antinociceptive effect.