Antinociception in bulboreticular neurons of the rat produced by spinally administered medetomidine, an alpha 2-adrenoceptor agonist.
The aim of this investigation was to evaluate if spinal alpha 2-adrenergic mechanisms modulate the nociceptive input to the medial bulboreticular formation. The effect of intrathecal (i.t.) medetomidine, a highly selective alpha 2-adrenoceptor agonist, was studied on peripherally evoked stimulation of the nociceptive bulboreticular formation neurons of the rat. The response to stimulation of the hind- and forepaw was evaluated separately in the same neurons before and after i.t. application of medetomidine from the catheter located at the lumbar level. Medetomidine i.t. produced a dose-dependent (2.5-7.5 micrograms) suppression of the nociceptive responses, and this suppression was completely reversed by i.p. atipamezole (1.5 mg/kg), a highly selective alpha 2-adrenoceptor antagonist. The average i.t. dose of medetomidine needed to produce 50% suppression was 2.2 micrograms for the hindpaw-elicited responses and 4.5 micrograms for the forepaw-elicited responses. Maximal suppression was obtained within 10 min and lasted for at least 60 min. When applied systemically (i.p.), much higher doses of medetomidine were needed for suppression of responses to the neuronal population studied (155 micrograms/kg of medetomidine needed to produce a 50% suppression of the evoked response). The results suggest that medetomidine can significantly attenuate nociceptive input to the medial bulboreticular formation due to spinal alpha 2-adrenergic mechanisms.
Department of Physiology, University of Helsinki, Finland.
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Pertovaara
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D007278:Injections, Spinal; D020926:Medetomidine; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine