Recent studies of the trigeminal brain stem nuclear complex have served to reinforce the classic concept of the involvement the spinal trigeminal nucleus (STN), especially its caudal component, subnucleus caudalis, as the essential brain stem release of orofacial nociceptive information to higher levels of the brain. Although a great deal of information is available concerning the anatomy and connections of the STN, no data is available regarding the major neurotransmitters that subserve STN protections. Until such data is obtained little progress can be made toward understanding the pharmacology and biochemistry of this system. The major goals are to investigate the possible presence of several putative neurotransmitters in the STN utilizing novel monoclonal antibodies in conjunction with immunohistochemistry and to evaluate which of these neurotransmitters are associated with the major efferent projections of this nucleus. These goals are defined by the following specific objectives: 1) to establish whether aspartate or cysteic acid containing neurons are present in the STN and to determine whether they comprise neuroral populations which are separate from glutamatergic neurons: 2) to determine if the trigeminothalamic, trigeminospinal, trigeminocollicular or trigeminocerebellar projections arise from glutamate and/or aspartate containing neurons; 3) to evaluate the chemical nature of synaptic inputs onto excitatory amino acid-containing STN neurons which project to the thalamus, spinal cord or other areas utilizing combined electron microscopic-immunohistochemical-immunoautoradiography; and 4) to raise monoclonal antibodies to the putative transmitters taurine, cysteine sulfinic acid, quinolinic acid, aspartyl-glutamate and glutamyl-taurine and if successful to establish whether STN neurons contain any of these substances. The proposed investigation will provide important and novel data concerning the neurotransmitters utilized by STN neurons and will establish a basic foundation for future biochemical and pharmacological studies that may ultimately lead to better therapeutic management of orofacial pain.
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