The ventrolateral medulla of the rat is connected with the spinal cord dorsal horn by an indirect descending pathway relayed in the A5 noradrenergic cell group.

The pathway conveying the descending inhibitory noradrenergic input elicited from the caudal ventrolateral medulla (VLM) onto the spinal cord dorsal horn was studied in the rat. Retrograde labeling with cholera toxin subunit B (CTb) injected into the dorsal horn was combined with immunostaining for dopamine-beta-hydroxylase (DBH) in the VLM and other brainstem nuclei containing noradrenergic cells. CTb-labeled neurons occurred in the lateral part of the VLM (VLMlat), located ventrolaterally to the DBH-immunoreactive cells of the A1 noradrenergic cell group. Neuronal profiles stained for CTb and DBH (double labeled) occurred in the A5 (31%), A6 (57%), and A7 (12%) noradrenergic cell groups. To ascertain whether noradrenergic cells targeting the spinal cord in those groups received projections from the VLMlat, this area was injected with the anterograde tracer biotinylated dextran amine (BDA). Labeled terminal fibers with boutons en passant were apposed to numerous double-stained neurons in the A5 cell group. Similar appositions occurred in small amounts in the ventral subcoerulear component of the A6. Correlated light and electron microscopic analyses of the labeled appositions revealed that the BDA-labeled axonal boutons contained spherical vesicles and were presynaptic at asymmetrical contacts to somata and dendritic profiles of the double-stained A5 neurons. These data indicate the occurrence of an indirect dysynaptic pathway connecting the VLM to the spinal cord, with a relay in the A5 cells. This pathway may convey the antinociceptive effects mediated by alpha 2-adrenoreceptors, which have been previously observed in the spinal cord following VLM stimulation.