Abstract
Neurons located in the nucleus raphe magnus (NRM), a region important in the control of nociception, appear to be tonically inhibited by noradrenergic (NA) neurons. Anatomical studies have suggested that the A5 catecholamine nucleus may be the primary source of noradrenergic neurons whose terminals are located in the NRM. The purpose of the present study was to examine the role of A5 neurons in the modulation of nociception. Bilateral electrolytic lesions of the A5 nuclei produced a marked and long-lasting antinociception as assessed by both the tail-flick and hot-plate tests. Unilateral A5 lesions also produced a long-lasting elevation in hot-plate latency, but the elevation of tail-flick latency was smaller in magnitude and was only observed one day following the lesion. This finding is consistent with previous studies which have shown that blockade of the NA input to the NRM by the microinjection of NA antagonists also produces antinociception. These data indicate that neurons located in the A5 nucleus may be the origin of this NA projection to the NRM. The elevation in tail-flick latency observed following A5 lesions was significantly attenuated by the intrathecal injection either the NA antagonist phentolamine or the serotonergic antagonist methylsergide. However, the elevation in hot-plate latency was not significantly altered by these monoaminergic antagonists. Similarly, previous studies have shown that the elevation in tail-flick, but not hot-plate latency, produced by the microinjection of NA antagonists in the NRM is attenuated by the intrathecal injection of either phentolamine or methysergide. These data suggest that the antinociception induced by lesions in the A5 region is mediated, at least in part, by the activation of spinally-projecting NA and serotonergic pathways. The results of these studies lead to the suggestion that the NA neurons located in the A5 modulate nociception by tonically inhibiting raphe-spinal neurons located in the NRM.
