Alpha-adrenergic receptor agonists, but not antagonists, alter the tail-flick latency when microinjected into the rostral ventromedial medulla of the lightly anesthetized rat.

The present experiments, part of an ongoing study designed to characterise the role of norepinephrine (NE) in regulating the activity of putative nociceptive modulatory neurons in the rostral ventromedial medulla (RVM), assessed the effects of alpha-adrenergic receptor-selective agents on the nociceptive threshold (as measured by the tail-flick withdrawal response on noxious heat). These microinjection studies were carried out in the barbiturate-anesthetized rat, a preparation which is favourable for acute neurophysiological studies. The data obtained demonstrate that, as observed by others in the awake animal, activation of alpha 2-adrenergic receptors in the RVM produces hypoalgesia. However, unlike in the awake animal, when antagonists selective for either the alpha 1- or alpha 2-adrenergic receptor are microinjected alone into the RVM there is no change in the nociceptive threshold. These data suggest that the alpha 2-adrenergic receptor has a postsynaptic location and that barbiturate anaesthesia suppresses a tonically active or noxious stimulus-activated noradrenergic input to the RVM that is present in the awake animal.