[Antinociceptive effects of alpha(2)-adrenoceptor agonists ("analgesic" actions in animal experiments)agonists ("analgesic" actions in animal experiments).].

Der Schmerz
I Jurna

Abstract

alpha(2)-Adrenoceptor agonists like clonidine, dexmedetomidine, and ST-91, inhibit nociceptive reflex activity predominantly by a spinal mode of action. They mimic the action of the inhibitory transmitter noradrenaline, which is released from the terminals of bulbospinal monoaminergic pathways. The inhibition by noradrenaline is due partly to hyperpolarization of the postsynaptic neuronal membrane; however, the selective antinociceptive effect of the alpha(2)-adrenoceptor agonists results from reduction of the release of the excitatory transmitters such as glutamate and substance P, blockade of the binding of substance P to spinal neurones, and enhancement of the action of the inhibitory transmitter, 5-hydroxytryptamine. Clonidine and dexmedetomidine stimulate adrenoceptors of the alpha(2A) subtype, while ST-91 stimulates alpha(2B) adrenoceptors. Antinociception is manifested not only by depression of nociceptive reflexes and behaviour, but also by inhibition of the expression of immediate early genes in dorsal horn neurones following noxious stimulation. The inhibitory control from the brain stem of spinal nociceptive activity can be triggered by alpha(2)-adrenoceptor agonists. Moreover, impulse conduction in C fibres of perip...Continue Reading

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