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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Schools of Medicine
United States
Zip Code
Byers, Margaret R; Westenbroek, Ruth E (2011) Odontoblasts in developing, mature and ageing rat teeth have multiple phenotypes that variably express all nine voltage-gated sodium channels. Arch Oral Biol 56:1199-220
Veerayutthwilai, O; Byers, M R; Pham, T-T T et al. (2007) Differential regulation of immune responses by odontoblasts. Oral Microbiol Immunol 22:5-13
Veerayutthwilai, Orapin; Luis, Nadyne A; Crumpton, Rosa M et al. (2006) Peripherin- and CGRP-immunoreactive nerve fibers in rat molars have different locations and developmental timing. Arch Oral Biol 51:748-60
Heyeraas, K J; Kim, S; Raab, W H et al. (1994) Effect of electrical tooth stimulation on blood flow, interstitial fluid pressure and substance P and CGRP-immunoreactive nerve fibers in the low compliant cat dental pulp. Microvasc Res 47:329-43
Sugaya, A; Chudler, E H; Byers, M R (1994) Uptake of exogenous fluorescent Di-I by intact junctional epithelium of adult rats allows retrograde labeling of trigeminal sensory neurons. Brain Res 653:330-4
Redd, P E; Byers, M R (1994) Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide. J Periodontal Res 29:214-24
Nahin, R L; Byers, M R (1994) Adjuvant-induced inflammation of rat paw is associated with altered calcitonin gene-related peptide immunoreactivity within cell bodies and peripheral endings of primary afferent neurons. J Comp Neurol 349:475-85
Byers, M R (1994) Dynamic plasticity of dental sensory nerve structure and cytochemistry. Arch Oral Biol 39 Suppl:13S-21S
Byers, M R; Taylor, P E (1993) Effect of sensory denervation on the response of rat molar pulp to exposure injury. J Dent Res 72:613-8
Heyeraas, K J; Kvinnsland, I; Byers, M R et al. (1993) Nerve fibers immunoreactive to protein gene product 9.5, calcitonin gene-related peptide, substance P, and neuropeptide Y in the dental pulp, periodontal ligament, and gingiva in cats. Acta Odontol Scand 51:207-21

Showing the most recent 10 out of 38 publications