The overall objective is to improve our understanding of the sensory neurobiology of normal and pathologic dental tissue as a basis for improved dental diagnosis and treatment. Immunocytochemical studies in rats are designed to examine the structure and cytochemistry of normal dental innervation; to analyze neural reactions to dental injury and inflammation, including interactions between nerve fibers, immune cells, and pulpal healing rates; to study the mechanisms of peripheral nerve sprouting in relation to growth factors, nerve impulse inhibitors, or extracellular matrix molecules; and to correlate peripheral sprouting with possible alterations of the affected trigeminal axons and nerve cell bodies. In addition, physiological studies of axons in trigeminal nerves of ferrets and cats will examine possible changes in sensory and anesthetic properties of inflamed teeth. Finally, immunocytochemistry of normal extracted human teeth will be compared with the animal studies. For normal rat dental innervation we will continue immunocytochemical LM and EM analyses of various neuropeptides, transmitters and enzymes to gain better information on the types of nerve fibers innervating teeth and periodontium, their receptor distribution, their support cell associations, and whether or not they are immunoreactive for nerve growth factor receptor. For studies of nerve sprouting, three types of injury to rat molars will be done: shallow cavities; small pulp exposures causing limited pulpitis; and large occlusal exposures causing irreversible pulpitis. The effects of sensory or sympathetic denervation on surviving nerve fibers, on immune cell invasion and on pulpal healing rates will be analyzed for the three injuries, as will the effects of anti-inflammatory drugs. To study mechanisms of dental nerve sprouting, slow release carriers containing growth factors, tetrodotoxin, or laminin will be implanted into rat molars, and the degree of sprouting measured in relation to pulpal and immune cell responses. In some cases retrograde transport of WGA-HRP or I 125- NGF will be done to allow specific immunocytochemical studies of the cell bodies of the affected nerve fibers. In ferrets and cats we will induce inflammation in one canine tooth and then record from single fibers in alveolar nerve to analyze sensory properties of A and C fibers and their response to local anesthesia compared with contralateral control teeth. These experimental studies of normal and pathologic dental innervation will have significance for somatosensory neurobiology, neuro-immune interaction, neural plasticity, basic mechanisms of inflammation and healing, and diagnosis and treatment of dental pain.
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