Serotoninergic medullary raphespinal projection to the lumbar spinal cord in the rat: a retrograde immunohistochemical study

Classically the raphespinal system has been regarded as a serotoninergic system; inhibition of spinal nociceptive transmission produced by stimulation of the medullary raphe nuclei is mediated partially by spinal serotoninergic receptors. However, recent evidence suggests that the raphe nuclei are not homogeneous populations of serotoninergic cells. The objective of the present study was to re-examine, in the rat, the serotoninergic raphespinal projection to the lumbar spinal cord, and to determine the relative contribution of serotoninergic raphespinal neurons to the total population of raphespinal neurons. Microinjections of wheat-germ agglutinin horseradish peroxidase conjugate coupled to colloidal gold into the lumbar spinal cord resulted in the retrograde labeling of 53% and 59% of the serotoninergic neurons in the raphe nuclei and in the para-raphe zone, respectively. Conversely, 47% and 28% of the retrogradely labeled neurons in the raphe and para-raphe zone, respectively, demonstrated serotonin-like immunoreactivity. Thus, contrary to previous reports, the present results suggest 1) that only about half of the serotoninergic neurons in the raphe nuclei and in the surrounding para-raphe zone project to the lumbar spinal cord, and 2) that a large proportion of the neurons in the raphe nuclei (53%) and in the surrounding para-raphe zone (72%) that project to the lumbar spinal cord are not serotoninergic.