The projections of noradrenergic neurons in the A5 catecholamine cell group to the spinal cord in the rat: anatomical evidence that A5 neurons modulate nociception.

Brainstem noradrenergic neurons located in the A5, A6, and A7 catecholamine cell groups provide the entire noradrenergic innervation of the spinal cord. We have previously demonstrated that noradrenergic neurons in the A6 and A7 cell groups innervate the ventral and dorsal horns, respectively. Since the specific spinal cord terminations of the A5 cell group have not been clearly delineated, the present experiments were designed to trace the projections from this noradrenergic cell group to the spinal cord, using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with dopamine-beta-hydroxylase immunocytochemistry. The results of these experiments indicate that A5 noradrenergic neurons project ipsilaterally through the dorsolateral funiculus in cervical, thoracic, and lumbar segments. In cervical segments, these axons terminate primarily in the ipsilateral deep dorsal horn (laminae IV-VI) and the intermediate zone (lamina VII). In thoracic segments, the intermediolateral cell column is heavily innervated by A5 axons. In lumbar segments, the concentration of A5 axons is more diffuse and more widely distributed than that in cervical and thoracic segments. Although there is a higher density of axons in the deep dorsal horn and the intermediate zone, there are also scattered axons in the dorsal and ventral horns. The innervation of these regions of the spinal cord by A5 neurons provides anatomical support for the conclusion that these noradrenergic neurons are involved in modulating cardiovascular reflexes and nociceptive transmission in the spinal cord.