Little is known about the molecular mechanisms that cause excitation of neurons which innervate the teeth. We investigated whether rat dental sensory neurons express the vanilloid (capsaicin) receptor (VR1). Dental sensory neurons were identified by retrograde transport of the fluorescent dye DiIC18 placed in maxillary molars. Patch-clamp recordings in culture showed that 65% of DiIC18-labeled rat trigeminal ganglion neurons are excited by capsaicin. Responders covered the entire range of cell sizes examined (soma diameter, 24 to 48 μm). All non-responders had a soma diameter > 33 μm. Capsazepine (1 μM) reduced the capsaicin-evoked membrane current (6/6) and depolarization (7/7 responders). RT-PCR amplified a 375-bp product from DiIC18-labeled neurons which was identical to that expected for VR1. Thus, many rat dental primary afferent neurons are excited by capsaicin, and the response appears to be mediated by VR1. These results suggest that pharmacological blockers of VR1 may provide significant relief of dental pain.
Baumann TK (1993). Cultures of adult trigeminal ganglion neurons . In: In vitro biological models. Methods in toxicology. Vol. 1. Tyson CA, Frazier JM, editors. New York: Academic Press, pp. 61-69.
2.
Baumann TK, Martenson ME (2000). Extracellular protons both increase the activity and reduce the conductance of capsaicin-gated channels. J Neurosci 20:RC-80, 1-5.
3.
Baumann TK, Burchiel KJ, Ingram SL, Martenson ME (1996). Responses of adult human dorsal root ganglion neurons in culture to capsaicin and low pH. Pain65:31-38.
4.
Bevan S., Hothi S., Hughes G., James IF, Rang HP, Shah K., et al. (1992). Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. Br J Pharmacol107:544-552.
5.
Byers MR (1984). Dental sensory receptors. Int Rev Neurobiol25:39-94.
Caterina MJ, Schumacher MA, Tominaga M., Rosen TA, Levine JD, Julius D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature389:816-824.
8.
Eckert SP, Taddese A., McCleskey EW (1997). Isolation and culture of rat sensory neurons having distinct sensory modalities. J Neurosci Meth77:183-190.
9.
Hamill OP, Marty E., Neher E., Sakmann J., Sigworth F. (1981). Improved patch clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pfliigers Arch Eur J Physiol391:85-100.
10.
Harper AA, Lawson SN (1985). Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones. J Physiol (Lond)359:31-46.
11.
Hashimoto S., Maeda M., Yamakita J., Nakamura Y. (1990). Effects of zinc oxide-eugenol on leucocyte number and lipoxygenase products in artificially inflamed rat dental pulp. Arch Oral Biol35:87-93.
12.
Hwang SW, Cho H., Kwak J., Lee SY, Kang CJ, Jung J., et al. (2000). Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci USA97:6155-6160.
13.
Ichikawa H., Sugimoto T. (2000). Vanilloid receptor 1-like receptor-immunoreactive primary sensory neurons in the rat trigeminal nervous system. Neuroscience101:719-725.
14.
Ikeda H., Tokita Y., Suda H. ( 1997). Capsaicin-sensitive A delta fibers in cat tooth pulp . J Dent Res76:1341-1349.
15.
Liu L., Simon SA (1994). A rapid capsaicin-activated current in rat trigeminal ganglion neurons. Proc Natl Acad Sci USA91:738-741.
16.
Liu L., Simon SA (1996). Similarities and differences in the currents activated by capsaicin, piperine, and zingerone in rat trigeminal ganglion cells. J Neurophysiol76:1858-1869.
17.
Lopshire JC, Nicol GD (1998). The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies. J Neurosci18:6081-6092.
18.
Martenson ME, Arguelles JH, Baumann TK (1997). Enhancement of rat trigeminal ganglion neuron responses to piperine in a low-pH environment and block by capsazepine. Brain Res761:71-76.
19.
Matthews B., Wanachantararak S. (2000). Labeling toothpulp neurons in the trigeminal ganglion of the rat. Soc Neurosci Abstr26:948.
20.
Nair PN ( 1995). Neural elements in dental pulp and dentin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod80:710-719.
21.
Narhi M., Jyvasjarvi E., Virtanen A., Huopaniemi T., Ngassapa D., Hirvonen T. (1992). Role of intradental A- and C-type nerve fibres in dental pain mechanisms. Proc Finn Dent Soc88(Suppl 1):507-516.
22.
Narhi M., Yamamoto H., Ngassapa D., Hirvonen T. (1994). The neurophysiological basis and the role of inflammatory reactions in dentine hypersensitivity [review]. Arch Oral Biol39(Suppl):23S-30S.
23.
Petersen M., LaMotte RH, Klusch A., Kniffki KD (1996). Multiple capsaicin-evoked currents in isolated rat sensory neurons. Neuroscience75:495-505.
24.
Tominaga M., Caterina MJ, Malmberg AB, Rosen TA, Gilbert H., Skinner K., et al. (1998). The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron21:531-543.
25.
Vyklicky L., Knotkova-Urbancova H., Vitaskova Z., Vlachova V., Kress M., Reeh PW ( 1998). Inflammatory mediators at acidic pH activate capsaicin receptors in cultured sensory neurons from newborn rats. J Neurophysiol79:670-676.
