Effects of clonidine on neuronal firing evoked by a noxious stimulus.
When norepinephrine was applied microiontophoretically to certain neurons in the pontine reticular formation of rats, it produced an increase in neuronal firing like that produced by noxious stimulation. Previous studies have shown that both noxious stimulus- and norepinephrine-evoked increases in neuronal firing are mediated by alpha-adrenoceptors. These neurons were unresponsive to non-noxious stimuli, suggesting that they might play a role in nociception. Microiontophoretic or systemic administration of the selective alpha 2-adrenoceptor agonist clonidine significantly attenuated noxious stimulus-evoked firing, but had little effect on firing evoked by norepinephrine. This effect of clonidine could be prevented by the alpha 2-adrenoceptor antagonists piperoxan and yohimbine. These antagonists, when given alone, increased noxious stimulus-evoked firing, but had no effect on firing evoked by norepinephrine. In contrast, the selective alpha 1-adrenoceptor antagonist ARC-239 (2-(2,4-(o-methoxyphenyl)-piperazin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4) isoquinolindione dihydrochloride) attenuated both noxious stimulus- and norepinephrine-evoked firing. These data are consistent with the hypothesis that presynaptic alpha 2-adrenoceptors modulate the release of norepinephrine. Furthermore, these data suggest that the pontine reticular formation is one site at which clonidine could act to produce analgesia.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004594:Electrophysiology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010146:Pain; D010812:Physical Stimulation; D010879:Piperazines; D010883:Piperoxan / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D015016:Yohimbine / Q000494:pharmacology
D007546:Isoquinolines; D010879:Piperazines; D015016:Yohimbine; D010883:Piperoxan; C032994:AR-C239; D003000:Clonidine; D009638:Norepinephrine