Oral trigeminal stimulation by acids is involved in the consumption of many beverages and food items. It also signals the presence of noxious substances or pathologies (e.g., inflammation) in the mouth. The mechanisms by which the trigeminal nerve transduces and encodes chemical stimuli is not well understood. Using acids as a relevant class of stimuli, this work seeks to elucidate oral chemonociception and place it in the context of what is understood about cutaneous nociception. The first aim is to understand how the lingual epithelium contributes to or modulates the trigeminal response to acids. Data from neural recordings, transepithelial current measurements and physicochemical characteristics of acids will be correlated to determine the role of the lingual epithelium in the access to and direct stimulation of free nerve endings. These experiments will determine if damage-induced processes are involved. The second aim is to determine how acid stimuli are encoded by the trigeminal system. Single neuron recordings will be obtained in response to a number of acids (strong and weak, including C02) and other chemical trigeminal stimuli as well as to other modalities (heat, cold, and mechanical) of trigeminal stimuli. By classifying neurons according to their response profile, hypotheses concerning the coding of acid stimuli by different types of nociceptors will be tested. Specific transduction mechanisms and coding schemes will further be supported or rejected by studying interactions between acidic and other trigeminal stimuli. The third aim examines the role of several specific mechanisms (H+ sensitive K-channels and carbonic anhydrase-dependent acidification of the epithelium by C02) in conferring chemosensitivity on trigeminal endings. The presence of these and other mechanisms, inferred from initial studies and the literature, will be tested by measuring neural responses to acidic stimuli during pharmacological manipulation of the lingual epithelium. In conjunction with the findings from the neurophysiological studies, cellular localization of carbonic anhydrase and several nociceptive neuropeptides will be used to: a) resolve the relative contribution of neuronal and non-neuronal elements of the epithelium to chemosensitivity; and b) resolve whether some or all acidic stimuli are coded by the same population of nociceptive fibers that respond to endogenous compounds involved in nociceptive processes.