The Role of Alpha-2 Adrenergic Receptors in the Action of Anesthetics and Analgesics

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The present study was designed to examine the role of central noradrenergic system, especially alpha-2 adrenergic receptors in the action of various anesthetics and analgesics;nitrous oxide 75%, halothane 1.3%, pentobarbital 80mg/kg (ip), and morphine 5mg/kg (iv). Male Wistar rats were used. Analgesic effects of drugs were evaluated by the tail-flick test and response latencies were expressed as the percentage of the maximal possible effect (%MPE). Effects of combined use of alpha-2 adrenergic agonist, clonidine (150mug/kg), were also examined. Noradrenaline concentrations and alpha-2 receptor bindings in the brain and spinal cord were measured, using high performance liquid chromatography and "in vitro" receptor autroadiography (ligand ; [_3H]-clonidine). Modulation of analgesic effect of nitrous oxide by a stress (capture in the steel nets), lesion to the locus coeruleus, and anloxone were also examined.Nitrous oxide and morphine produced analgesia (%MPE 60% and 100%, ), but neither halothane nor pentobarbital did. Clonidine produced analgesia (%MPE 20-40%) in the awake rat. When it was comined with nitrous oxide, analgesic effect of nitrous oxide was sustained. With halothane and pentobarbital, it produced analgesia (%MPE 60-75% and 80-100%). In nitrous oxide-induced analgesia, there was a decrease in noradrenaline concentration and an increase in the binding of [_3H]-clonidine in the locus coeruleus and dorsal horn of the spinal cord. Locus coeruleuslesion markedly attenuated nitrous oxide-induced analgesia, while neither naloxone nor stress attenuated it.It is concluded that clonidine produces (or potentiates) analgesic effects of various drugs and that the analgesic effect of nitrous oxide is attributed to the effect on the central noradrenergic system, possibly by an activation of the descending inhibitory system and/or inhibition of the primary sensory afferent neuron via alpha-2 adrenergic receptors.