Effect of intrathecally administered noradrenergic antagonists on nociception in the rat.

Recent evidence suggests that some groups of noradrenergic neurons found in the brainstem have axonal connections in the spinal cord dorsal horn and may be involved in the control of pain sensitivity. Such evidence includes the demonstration that intrathecal injection of noradrenergic agonists increases nociceptive threshold (hypoalgesia). The present studies examined whether the descending noradrenergic system is tonically active and, if so, what noradrenergic receptor subtypes mediate the actions of endogenously-released norepinephrine. These studies involved the measurement of nociceptive threshold before and after the intrathecal injection of noradrenergic antagonists having different relative affinities for alpha-noradrenergic receptor subtypes. The intrathecal administration of alpha-noradrenergic antagonists produced a dose-dependent decrease in nociceptive threshold (hyperalgesia). This finding is consistent with the proposal that tonically-active bulbospinal noradrenergic neurons modulate the processing of nociceptive information in the spinal cord. The potency and duration of the hyperalgesia was correlated with the relative potency of the antagonists for the alpha-2 noradrenergic receptor. The relative potencies were as follows: yohimbine greater than phentolamine greater than WB 4101 greater than prazosin. Thus, endogenous norepinephrine which is tonically released from bulbospinal axon terminals may interact preferentially with noradrenergic receptors of the alpha-2 type.