The spinal trigeminal nucleus (STN), especially subnucleus caudalis, is an important component in the relay of orofacial nociceptive information to higher brain nuclei. Although many physiological studies have indicated the importance of this nucleus in orofacial nociception, very little anatomical data is available describing the relationships between two widely distributed putative excitatory neurotransmitters, glutamate and aspartate, and other transmitters in the STN. In particular, no electron microscopic immunohistochemical studies have been done to examine the relationship of either amino acid to STN projections or interconnections. An understanding of the distribution of these two amino acids in the STN will provide a basis for future biochemical and pharmacological studies of this region and may ultimately lead to better therapeutic management of orofacial pain. This project is designed to fulfill 3 long term objectives, which are: 1) to ultranstructurally analyze glutamate- and aspartate- containing neurons and processes in each subnucleus of the rat STN by using monoclonal antibodies that are specific for these 2 amino acids; 2) to elucidate the synaptic relationships and possible co-localization of glutamate and aspartate with other putative neurotransmitters and neuromodulators, including substance P, cholecystokinin, enkephalin and FMRF-amide; and 3) to use a retrograde-tract tracer, WGA-HRP, to determine whether the cells of origin of projections from the STN to the thalamus, cerebellum and spinal cord also contain glutamate and whether glutamate is involved in the trigeminal-thalamic-cortical pathway. These neurons will be characterized ultrastructurally and their involvement in both glutamatergic and substance P synapses described. The terminal arborization of projections from the STN to the above regions will also be examined ultrastructurally by using an anterograde tract tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), combined with electron microscopic immunohistochemical techniques to visualize glutamate. By achieving these objectives, a better understanding of both the neuroanatomical arrangement of the STN subnuclei and of the importance of excitatory amino acids in the cytoarchitecture of the STN will be gained. This information is essential to our understanding of the biochemical mechanisms underlying the relay of both orofacial pain and tactile sensations to other brain nuclei. This understanding may ultimately allow new and better treatments for the control of orofacial pain to be developed.
