The long term goal of this research is to develop methods for the prevention and treatment of dental pain, based on a better understanding of the membrane mechanisms which lead to the excitation of trigeminal primary afferent neurons by mechanical stimuli. Nociceptive neurons which innervate the teeth are excited by thermal, mechanical, osmotic, and chemical stimuli. Experimental evidence is consistent with the hydrodynamic theory of sensory transduction in the dentine. According to this theory, external stimuli (be they thermal, mechanical,or osmotic) are translated into movements of fluid in dentinal tubules, the movements deform sensory nerve endings and cause excitation of nociceptors. The hydrodynamic theory implies the presence of mechanosensitive transducer elements in trigeminal nerve endings. We hypothesize that the transducer elements are mechanosensitive ion channels. A wide variety of mechanosensitive ion channels are known to exist in different cell types, but thus far there have been no studies on such channels in trigeminal neurons. The goal of this research proposal is to characterize the properties of mechanosensitive ion channels in trigeminal ganglion neurons in general and in tooth afferent neurons in particular. Toothache can often be traced to an inflammation of the tooth pulp. Since tissue inflammation is known to cause the sensitization of nociceptive fibers to mechanical stimuli, the next goal of this research proposal is to determine if the operating characteristics of mechanosensitive ion channels in trigeminal ganglion neurons are altered by low extracellular pH or exposure to inflammatory mediators. Together these studies will contribute to a better understanding of the sensory/molecular events in which cause dental pain.
| Chaudhary, P; Martenson, M E; Baumann, T K (2001) Vanilloid receptor expression and capsaicin excitation of rat dental primary afferent neurons. J Dent Res 80:1518-23 |
| Baumann, T K; Martenson, M E (2000) Extracellular protons both increase the activity and reduce the conductance of capsaicin- gated channels. J Neurosci 20:RC80 |
