Psychophysical and neurobiological evidence that the oral sensation elicited by carbonated water is of chemogenic origin

The sensation produced by carbonated beverages has been attributed to chemi cal excitation of nociceptors in the oral cavity via the conversion of CO2 to carbonic acid in a reaction catalyzed by carbonic anhydrase. In separate studies, we tested if the carbonic anyhdrase blocker, acetazolamide, reduc ed either the intensity of sensation in humans or c-fos expression by trige minal neurons in rats, evoked by application of carbonated water to the ton gue. In the psychophysical experiment, one-half of the dorsal tongue was pr etreated with acetazolamide(1 or 2%), after which the tongue was exposed bi laterally to carbonated water. In a two-alternative forced-choice paradigm, subjects chose which side of the tongue yielded a stronger sensation and a dditionally rated the magnitude of sensation on each side. Pretreatment wit h acetazolamide reduced the magnitude of sensation elicited by carbonated w ater in a concentration-dependent manner, since a significant majority of s ubjects chose the untreated side of the tongue as having a stronger sensati on and assigned significantly higher intensity ratings to that side. Acetaz olamide did not affect the irritant sensation from citric acid, while capsa icin pretreatment reduced both the sensation elicited by carbonated water a nd the irritation induced by citric acid application. In a separate experim ent using rats, delivery of carbonated water to the tongue significantly in creased the number of cells expressing c-fos-like immunoreactivity in the d orsomedial trigeminal nucleus caudalis (versus saline controls); this was s ignificantly reduced by pretreatment with acetazolamide. Our results suppor t the hypothesis that carbonated water activates lingual nociceptors via co nversion of CO2 to carbonic acid; the nociceptors in turn excite trigeminal neurons involved in signaling oral irritation.