The overall goal of this research is to determine the cellular mechanisms responsible for chemical oral irritation. This will be achieved by obtaining single unit recordings from rat lingual and chorda tympani nerves, and patch-clamp recordings from rat trigeminal ganglion neurons in response to chemical irritants. The irritants include those found in spices such as red and black pepper, horseradish, ginger, mustard, cinnamon, and onions; and in pollutants such as acids, alcohols, aldehydes, and acetates. When placed on lingual epithelium, these compounds produce a variety of sensations that range from warm to burning to painful. Emphasis will be placed on determining the neural responses elicited by capsaicin, the pungent ingredient in ed pepper that has been shown to activate a subset of pain fibers. Capsazepine, a specific capsaicin receptor antagonist, will be used to determine whether responses occur through capsaicin- sensitive pathways. Olvanil and tinyatoxin will be used as non-pungent capsaicin analogues.
The specific aims i nclude determining: 1) whether irritation is caused only by the activation of a subset of lingual nerve pain fibers, 2) whether irritants activate chorda tympani fibers, 3) whether activation of lingual nerve fibers is a consequence only of the irritants' activation of capsaicin receptors, 4) whether the irritant-induced currents in isolated trigeminal ganglion cells are inhibited by capsazepine, 5) whether a specific current is associated with pungency, and 6) whether irritants can modulate chorda tympani responses to taste stimuli. This research will provide fundamental information relating to taste, irritation, and pain. Regarding issues of health, capsaicin and its analogues are used clinically in relieving trigeminal neuralgia and vasomotor rhinitis as well as other painful symptoms. Understanding the basic mechanisms of how irritants activate nerves could lead to the development of effective countermeasures against irritating stimuli.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Sensory Disorders and Language Study Section (CMS)
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Duke University
Schools of Medicine
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Tellez, Luis A; Perez, Isaac O; Simon, Sidney A et al. (2012) Transitions between sleep and feeding states in rat ventral striatum neurons. J Neurophysiol 108:1739-51
MacDonald, Christopher J; Meck, Warren H; Simon, Sidney A (2012) Distinct neural ensembles in the rat gustatory cortex encode salt and water tastes. J Physiol 590:3169-84
Tandon, Shashank; Simon, Sidney A; Nicolelis, Miguel A L (2012) Appetitive changes during salt deprivation are paralleled by widespread neuronal adaptations in nucleus accumbens, lateral hypothalamus, and central amygdala. J Neurophysiol 108:1089-105
Picazo-Juárez, Giovanni; Romero-Suárez, Silvina; Nieto-Posadas, Andrés et al. (2011) Identification of a binding motif in the S5 helix that confers cholesterol sensitivity to the TRPV1 ion channel. J Biol Chem 286:24966-76
Oliveira-Maia, A J; Roberts, C D; Simon, S A et al. (2011) Gustatory and reward brain circuits in the control of food intake. Adv Tech Stand Neurosurg 36:31-59
Oliveira-Maia, Albino J; Roberts, Craig D; Walker, Q David et al. (2011) Intravascular food reward. PLoS One 6:e24992
Gutierrez, Ranier; Simon, Sidney A (2011) Chemosensory processing in the taste - reward pathway. Flavour Fragr J 26:231-238
Rosenbaum, Tamara; Simon, Sidney A; Islas, Leon D (2010) Ion channels in analgesia research. Methods Mol Biol 617:223-36
Kuhn, Cynthia; Johnson, Misha; Thomae, Alex et al. (2010) The emergence of gonadal hormone influences on dopaminergic function during puberty. Horm Behav 58:122-37
Gutierrez, Ranier; Simon, Sidney A; Nicolelis, Miguel A L (2010) Licking-induced synchrony in the taste-reward circuit improves cue discrimination during learning. J Neurosci 30:287-303

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