Neurobiological and Psychophysical Mechanisms Underlying the Oral Sensation Produced by Carbonated Water

Abstract

Carbonated drinks elicit a sensation that is highly sought after, yet the underlying neural mechanisms are ill-defined. We hypothesize that CO(2) is converted via carbonic anhydrase into carbonic acid, which excites lingual nociceptors that project to the trigeminal nuclei. We investigated this hypothesis using three methodological approaches. Electrophysiological methods were used to record responses of single units located in superficial laminae of the dorsomedial aspect of trigeminal subnucleus caudalis (Vc) evoked by lingual application of carbonated water in anesthetized rats. After pretreatment of the tongue with the carbonic anhydrase inhibitor dorzolamide, neuronal responses to carbonated water were significantly attenuated, followed by recovery. Using c-Fos immunohistochemistry, we investigated the distribution of brainstem neurons activated by intraoral carbonated water. Fos-like immunoreactivity (FLI) was significantly higher in the superficial laminae of dorsomedial and ventrolateral Vc in animals treated with carbonated water versus controls. Dorzolamide pretreatment significantly reduced FLI in dorsomedial Vc. We also examined the sensation elicited by carbonated water in human psychophysical studies. When one side of the tongue was pretreated with dorzolamide, followed by bilateral application of carbonated water, a significant majority of subjects chose the untreated side as having a stronger sensation and assigned significantly higher intensity ratings to that side. Dorzolamide did not reduce irritation elicited by pentanoic acid. The present data support the hypothesis that carbonated water excites lingual nociceptors via a carbonic anhydrase-dependent process, in turn exciting neurons in Vc that are presumably involved in signaling oral irritant sensations.

Trigeminal Chemesthesis

“…Prototypical chemesthetic stimuli include many plant-based molecules such as (a) capsaicinoids (capsaicin from chili peppers (Szolcsányi and Jancsó-Gábor 1975;Stevens and Lawless 1987;Green 1989;Caterina et al, 1997; piperine from black pepper (Stevens and Lawless 1987;Green 1996;Dessirier et al, 1999)), (b) isothiocyantes (allyl isothiocyanate from mustard oil (Simons et al, 2003;Jordt et al, 2004;Bandell et al, 2004) and allicin from garlic (Bautista et al, 2005) and (c) the alkaloid nicotine (Jansco et al, 1961;Dessirier et al, 1997;, found in the nightshade family (Solanaceae) of plants. Ingestion of these compounds at low levels elicits a predominantly pungent or burning sensation from the oral mucosa (Keele 1962;Lawless and Stevens 1988;Rentmeister-Bryant and Green 1997) and vermilion border of the lips (Lawless 1984;Lawless and Stevens 1988), but have minor or no discernible taste qualities on their own (except for nicotine which has been described as bitter (Pfaffman 1959).…”

“…Importantly, it should be noted that salts and acids, which evoke sensations of saltiness and sourness, respectively, can elicit pungent sensations from the oral cavity (Simons et al, 1999;Dessirier et al, 2000b;2001) Simons et al, 2003b;Thuerauf et al, 2006), and outward-rectifying 2-pore potassium channels including KCNK3, KCNK9 and KCNK18 (Bautista et al, 2008). Most irritants interact with one of several ionotropic TRP channels including TRPA1, TRPM8, TRPV1, and TRPV2.…”

“…Psychophysical methods have been described that allow investigators to track oral irritation intensity across time (Lawless and Stevens 1988;Stevens and Lawless 1987;Green 1988;Dessirier et al, 1999Dessirier et al, , 2001Prescott 1999;Prescott and Stevenson 1996a;.…”

“…To date, many of the chemorirritants tested in psychophysical protocols evoke desensitizing patterns of oral irritation including capsaicin (e.g. Green 1989;1991;Szolcsányi 1990;Prescott 1999), piperine (Green 1996;Dessirier et al, 1999), ethanol (Prescott and Swain-Campbell 2000), acids (Dessirier et al, 2000b), salts (Dessirier et al, 2001), nicotine (Dessirier et al, 1997, allyl isothiocyanate (Simons et al, 2003a), cinnamic aldehyde (Prescott and Swain-Campbell 2000), zingerone (Prescott and Stevenson 1996a;, and menthol (Cliff and Green 1994;1996).…”

“…One potential solution that has been developed is the use of "half-tongue" methodologies (e.g. Dessirier et al, 1997;Simons et al, 1999) in which forced-choice, discrimination tasks are accomplished by placing a compound of interest on one side of a subject's tongue and the control solution on the other. Subjects can compare the sensation on both sides of the tongue simultaneously to identify any intensity differences.…”