Projections of substance P-immunoreactive neurons located in the ventromedial medulla to the A7 noradrenergic nucleus of the rat demonstrated using retrograde tracing combined with immunocytochemistry.

Stimulation of neurons located in the ventromedial medulla (VMM), including the nucleus raphe magnus (RMg), produces antinociception which appears to be mediated in part by activation of spinally-projecting noradrenergic neurons located in the A7 catecholamine nucleus. Although the identity of the VMM neurons that project to the A7 nucleus is not known, there is indirect evidence that these neurons contain substance P. This possibility was examined by injecting the retrograde tracer Fluoro-Gold into the A7 nucleus and determining whether substance P-immunoreactive neurons in the VMM were labeled with Fluoro-Gold. The results of these experiments demonstrated that numerous substance P-immunoreactive cells in the RMg, gigantocellular reticular nucleus pars alpha and the paragigantocellular reticular nucleus were retrogradely labeled by an injection of Fluoro-Gold into the A7 nucleus. These observations indicate that substance P-containing neurons in these areas of the VMM project to the A7 nucleus. Thus, the antinociception induced by stimulation of the VMM may be mediated by activation of substance P-containing neurons that project to and activate spinally projecting noradrenergic neurons in the A7 nucleus.