Afferent connections of the rostral medulla of the cat: a neural substrate for midbrain-medullary interactions in the modulation of pain.

In order to study the organization of the rostral medulla of the cat and its contribution to pain control mechanisms, we have examined the afferent connections of the midline nucleus raphe magnus (NRM), the laterally located nucleus reticularis magnocellularis (Rmc), and the nucleus reticularis gigantocellularis (Rgc) located dorsal to Rmc. Iontophoretic injections of HRP were made into the three regions; the distribution of retrogradely labeled neurons in brainstem and spinal cord was then mapped. While significant differences characterize the source of afferents to Rgc and NRM/Rmc, there is little to distinguish that between NRM and Rmc. The predominant spinal projection is to Rgc; fewer labeled neurons were recorded after injections into Rmc. In contrast, no significant direct spinal projection to NRM was found. All three regions receive input from widespread areas within the medullary and pontine reticular formation. The most pronounced differences in the distribution of retrogradely labeled neurons were found in the midbrain. The major projection to both NRM and Rmc derives from the periaqueductal gray (PAG) and from the adjacent nucleus cuneiformis. Labeled cells are concentrated in the dorsal and lateral PAG; few are found in the ventrolateral PAG. In contrast, Rgc receives few afferents from the PAG; however, after Rgc injections, many cells were recorded in the deep layers of the contralateral tectum. None of the injection sites produced significant labeling of the catecholamine-rich dorsolateral pontine tegmentum or of the nucleus raphe dorsalis. The demonstration of significant PAG projections to NRM/Rmc provides anatomical evidence for the hypothesis that opiate and stimulation-produced analgesia involves connections from PAG to neurons of NRM and Rmc which, in turn, inhibit spinal nociceptors.