This proposal intends to use the dental afferent-trigeminal system of felines to study the central effects of different peripheral lesions in the immature and mature system and relate these events to reorganization. Light (LM) and electron (EM) microscopic methods will be utilized following two procedures that result in transganglionic degeneration in the brain stem trigeminal nuclei (STN): 1) dental pulpectomies and 2) pulpal injections of optimal concentrations of a ricin cytotoxin. The study will also include subjects at ages of exfoliation of primary teeth and eruption of permanent ones (mixed-dentition). Ricin effects will be studied by LM and EM for fiber degeneration in the dental nerves and terminal and postsynaptic alterations centrally. Single canines will be used for lesions. Immunocytochemical localization (ICC-L) procedures will allow for identification of possible neurotransmitters involved, and horseradish peroxidase (HRP) will be used to evaluate neuronal transport patterns centrally. Patterns throughout STN will be studied by LM, but emphasis will be on the highly organized superficial layers of the medullary dorsal horn (MDH)/pars caudalis (PC). The study will compare kittens with primary/deciduous dentition, young cats with recently erupted permanent dentition and those with mixed dentition. The central changes will be studied at survivals of 7-14 days and chronically at 6-8 weeks after lesions. Emphasis will be on evaluation of degenerating classes and proportions of synaptic structures, dendritic processes involved, and evidence of remodeling at LM and EM levels. ICC-L will include antibodies to calcitonin gene-related peptide (CGRP), and somatostatin, and a plant lectin (Griffonia/I-B4) for primary afferents. Intrinsic pathways will be studied with antibodies to GABA (GAD), serotonin, enkephalin, neurotensin, and tyrosine. Remodeling will also be examined using HRP implants into mandibular teeth at 6-8 weeks following maxillary lesions in each age group. The central patterns for the HRP, degeneration, and ICC-L will be compared qualitatively, then an optical imaging system will be used to chart pattern changes in MDH/PC for HRP and ICC-L. The results should provide new information about central events coincident with peripheral lesions during development that may be associated with central remodeling. Finally, preliminary trials will be done to evaluate the use of another animal model, the ferret, for future studies.
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