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Cells within the ventral medulla whose axons descend to the spinal dorsal horn via the dorsolateral funiculus (DLF) play an important role in pain modulation. Previous evidence suggests that this pathway is primarily serotonergic. We have examined this hypothesis directly using combined retrograde horseradish peroxidase/serotonin immunohistochemical staining. Cells of the ventral medulla contributing to the DLF were found to be largely non-serotonergic. This result was confirmed by two approaches: by the absence of a significant number of double-labeled cells following discrete horseradish peroxidase labeling of the DLF and by the persistence of double-labeled cells in animals with DLF lesions made rostral to intraspinal injections of horseradish peroxidase solutions. The conclusion is made that the previously described nucleus raphe magnus-DLF-dorsal horn pathway is predominantly non-serotonergic.

Non-serotonergic origins of the dorsolateral funiculus in the rat ventral medulla