Direct projections from the midbrain periaqueductal gray and the dorsal raphe nucleus to the trigeminal sensory complex in the rat.

It is well known that analgesia can be produced by stimulation of the midbrain periaqueductal gray and dorsal raphe nucleus. This stimulation-produced analgesia may operate, at least partly, through direct projections to nociceptors in the primary sensory nuclei. In the present study, direct projections from the midbrain periaqueductal gray and dorsal raphe nucleus to the trigeminal sensory complex were studied in the rat. After injection of Phaseolus vulgaris leucoagglutinin into the periaqueductal gray or dorsal raphe nucleus, terminal labeling was found in the principal sensory trigeminal nucleus and the oral, interpolar and caudal subnuclei of the spinal trigeminal nucleus, bilaterally with an ipsilateral predominance. The terminal labeling was prominent in the ventrolateral parts of the trigeminal sensory complex; it was particularly marked in the principal sensory trigeminal nucleus and laminae I and III of the caudal subnucleus of the spinal trigeminal nucleus. After injection of cholera toxin B subunit into the principal sensory trigeminal nucleus or one of the subnuclei of the spinal trigeminal nucleus, retrogradely labeled cells were seen in the periaqueductal gray and dorsal raphe nucleus, bilaterally with an ipsilateral dominance. In the periaqueductal gray they were most often seen in the ventrolateral and dorsolateral subdivisions, but no particular topographic organization was detected in the distribution of retrogradely labeled neurons in the periaqueductal gray and dorsal raphe nucleus after tracer injection into each subdivision of the trigeminal sensory complex. After injections of Fast Blue and Diamidino Yellow, respectively, into the principal sensory trigeminal nucleus and the caudal subnucleus of the spinal trigeminal nucleus on one side of the brain, a number of doubly labeled neurons were found in the periaqueductal gray and dorsal raphe nucleus, bilaterally with an ipsilateral dominance. The results indicate that a considerable number of neurons in the periaqueductal gray and dorsal raphe nucleus send projection fibers to the trigeminal sensory complex, and that some of them send their axons to both the principal sensory trigeminal nucleus and the caudal subdivision of the spinal trigeminal nucleus by way of axon collaterals. These projections may subserve suppression of the activity of nociceptive neurons in the trigeminal system.