The innervation of the pulp-dentin complex is of major health importance because it mediates dental pain and serves poorly understood functions in maintaining the vitality of teeth and in inflammation and repair of dental tissues. Moreover, mammalian teeth are intriguing targets of sensory innervation because of their late (postnatal) development and because they have a rich nociceptive innervation confined within a rigid well-defined pulp chamber. In order to develop therapeutic strategies, it is essential that the biological properties of neurons that innervate the dental pulp be better defined. Thus, the long-term objective of this research program is to define the extent to which the dental pulp and its innervation interact during development and in response to injury, and ultimately to elucidate the mechanisms for this interaction. The underlying hypothesis is that specific neurotrophic factors act as mediators by which dental tissues selectively influence the different subpopulations of sensory neurons that innervate them. Work in this laboratory has demonstrated that one class of dental sensory neurons fails to develop in response to postnatal deprivation of one such factor, nerve growth factor. The goals of the proposed studies are to (1) determine how many distinct populations of sensory neurons supply the dental pulp and to define the phenotypic features of these populations, (2) develop and utilize an experimental system that permits assessment of responses to tooth injury by sensory neurons, and (3) characterize expression of neurotrophic signals by non-neural pulp cells. Trigeminal neurons that project to the molar pulp in the rat will be identified by application of a persistent retrograde tracer under conditions that minimize injury and allow for complete healing. This will permit precise characterization of dental neurons with respect to (a) morphology, (b) expression of cytochemical markers, and (c) the specific neurotrophic factor to which they are potentially responsive. In order to identify neuronal responses to tooth injury, the same parameters will be examined over time in neurons that have been labeled before the pulp-dentin complex is subjected to injuries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009137-10
Application #
6749492
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Kusiak, John W
Project Start
1991-02-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
10
Fiscal Year
2004
Total Cost
$105,450
Indirect Cost
Name
University of Mississippi Medical Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Yang, Hong; Bernanke, Jayne M; Naftel, John P (2006) Immunocytochemical evidence that most sensory neurons of the rat molar pulp express receptors for both glial cell line-derived neurotrophic factor and nerve growth factor. Arch Oral Biol 51:69-78
Pan, Yan; Wheeler, Esther F; Bernanke, Jayne M et al. (2003) A model experimental system for monitoring changes in sensory neuron phenotype evoked by tooth injury. J Neurosci Methods 126:99-109
Pan, M; Naftel, J P; Wheeler, E F (2000) Effects of deprivation of neonatal nerve growth factor on the expression of neurotrophin receptors and brain-derived neurotrophic factor by dental pulp afferents of the adult rat. Arch Oral Biol 45:387-99
Naftel, J P; Richards, L P; Pan, M et al. (1999) Course and composition of the nerves that supply the mandibular teeth of the rat. Anat Rec 256:433-47
Wheeler, E F; Naftel, J P; Pan, M et al. (1998) Neurotrophin receptor expression is induced in a subpopulation of trigeminal neurons that label by retrograde transport of NGF or fluoro-gold following tooth injury. Brain Res Mol Brain Res 61:23-38
Qian, X B; Naftel, J P (1996) Effects of neonatal exposure to anti-nerve growth factor on the number and size distribution of trigeminal neurones projecting to the molar dental pulp in rats. Arch Oral Biol 41:359-67
Naftel, J P; Qian, X B; Bernanke, J M (1994) Effects of postnatal anti-nerve growth factor serum exposure on development of apical nerves of the rat molar. Brain Res Dev Brain Res 80:54-62
Naftel, J P; Bernanke, J M; Qian, X B (1994) Quantitative study of the apical nerve fibers of adult and juvenile rat molars. Anat Rec 238:507-16
Qian, X B; Naftel, J P (1994) The effects of anti-nerve growth factor on retrograde labelling of superior cervical ganglion neurones projecting to the molar pulp in the rat. Arch Oral Biol 39:1041-7