The role of descending noradrenergic systems in regulation of nociception: the effects of intrathecally administeredt α-adrenoceptor antagonists and clonidine

Abstract

It has been proposed that descending noradrenergic systems exercise a tonic inhibition of nociception at the spinal level. The recent finding that changes in tail skin temperature (TT) may have a strong effect on the tail-flick latency makes a reevaluation of this hypothesis necessary. The α-adrenoceptor agonist clonidine injected intrathecally (i.th.) in a dose of 60 μg increased the response temperature in the increasing hot plate test 10 min after injection, and prolonged the tail-flick latency 30–60 min after injection. A considerable part of the change in tail-flick latency was caused by a reduction in TT. The α 1-antagonist prazosin (30 and 60 μg) tended to increase the response temperature in the increasing hot plate test after 60 min, and to prolong the latency in the tail-flick test. These effects were not statistically significant. Clonidine and prazosin induced sensorimotor impairment and a reduction in body temperature after 30–60 min. The α 2-antagonist yohimbine had no effect in the increasing hot plate test, but reduced the tail-flick latency 10 min after drug administration. This reduction could be explained by an increase in TT. The results suggest that the reduced latency in the tail-flick test after i.th. injection of yohimbine is caused by an increase in the tail blood flow, and does not support the hypothesis of a tonic bulbospinal noradrenergic inhibition of nociception. The time course of response latencies suggests that supraspinal mechanisms may be involved in the effects of i.th. clonidine and prazosin in the tail-flick test, while there seems to be a spinally mediated antinociceptive effect of clonidine that can be demonstrated in the increasing hot plate test.