Oral Irritant Effects of Nicotine: Psychophysical Evidence for Decreased Sensation Following Repeated Application and Lack of Cross-desensitization to Capsaicin

Psychophysical methods were used to assess changes in the intensityof irritant sensations elicited by repeated application of capsaicinand nicotine delivered unilaterally to the tongue of human subjects.Whereas capsaicin (0.5 or 3 p.p.m.; repeated at 1 min intervalsover 10 min) evoked progressively stronger ratings of irritation(sensitization),there was a significant decrement in irritation ratings (desensitization)to repeated application of nicotine (0.1%). A two-alternativeforced-choice (2-AFC) procedure was additionally used to testfor self- and cross-desensitization. After the subjects hadreceived either repeated capsaicin or nicotine, a rest periodensued followed by the 2-AFC procedure. Either capsaicin ornicotine was delivered bilaterally to the tongue and subjectswere asked to choose which side yielded a stronger sensation.Following capsaicin pretreatment, subjects reported that capsaicinevoked a stronger sensation on the previously untreated side(capsaicin self-desensitization). Similar self-desensitizationwas observed with nicotine. Furthermore, nicotine evoked a significantlyweaker sensation on the side of the tongue pretreated with capsaicin(cross-desensitization). In contrast, capsaicin did not consistentlyevoke a weaker sensation on the nicotine-pretreated side, indicatingan absence of cross-desensitization. These results are discussedin terms of physiological mechanisms that might underlie thecontrasting sensory effects of nicotine versus capsaicin. Chem.Senses 22: 483–492, 1997.     

Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects.

Using a bipolar rating scale, human subjects rated the intensity of irritation sensation evoked by repeated application of piperine (75 p.p.m.) or nicotine (0.12%) to one side of the dorsal surface of the tongue. The intensity of irritation elicited by repeated application of piperine significantly increased, while irritation elicited by repeated nicotine significantly decreased. We additionally tested if nicotine or piperine desensitized the tongue. After either piperine or nicotine was repeatedly applied to one side of the tongue, a 5 or 10 min rest period ensued, followed by re-application of piperine or nicotine to both sides of the tongue. Subjects were asked to choose which side of the tongue gave rise to a stronger irritation in a two-alternative forced choice (2-AFC) paradigm. In addition, they gave separate ratings of the intensity of irritation on the two sides of the tongue. When piperine was applied bilaterally after unilateral pretreatment with piperine and a 10 min rest period, subjects consistently chose the non-pretreated side to yield stronger irritation and assigned significantly higher ratings to that side, indicative of piperine self-desensitization. A similar self-desensitization effect was found when bilateral application of nicotine followed unilateral treatment with nicotine and a 5 min rest period. Unilateral treatment with piperine also reduced nicotine-evoked irritation on the pretreated side (cross-desensitization), but treatment with nicotine did not affect piperine-evoked irritation. This asymmetrical cross-desensitization pattern is similar to that observed between capsaicin and nicotine and constitutes an additional similarity between piperine and capsaicin.     

Oral irritation by mustard oil: self-desensitization and cross-desensitization with capsaicin

We investigated the temporal pattern of oral irritation elicited by sequential application of mustard oil (allyl-isothiocyanate), and whether it exhibits self-desensitization and cross-desensitization with capsaicin. Mustard oil (0.125%, 40 micro l) was sequentially applied to one side of the tongue at 1 min intervals, and subjects rated the intensity of the irritant sensation elicited by each stimulus. Ratings successively declined across trials, indicating desensitization. In contrast, sequential application of capsaicin (10 ppm) elicited irritation that increased in intensity across trials (sensitization). To test for self-desensitization by mustard oil, a 10 min hiatus was imposed following the series of unilateral mustard oil stimuli, after which mustard oil was applied to both sides of the tongue. In a two-alternative forced-choice paradigm, subjects chose which side had stronger irritation and also independently rated the irritant intensity on each side. A significant majority of subjects chose the side not previously receiving mustard oil as more intense, and assigned significantly higher intensity ratings to that side, indicating self-desensitization. In two additional sessions, the same paradigm was used to show mustard oil cross-desensitization of irritation elicited by capsaicin, and capsaicin cross-desensitization of irritation from mustard oil. In a final session, sequential application of mustard oil at faster (20 s) intervals initially evoked a sensitizing pattern followed by desensitization. The temporal patterns of oral irritation exhibited by mustard oil, and its reciprocal cross-desensitization with capsaicin, are similar to those of menthol and nicotine.     

The oral sensation of carbonated water: cross-desensitization by capsaicin and potentiation by amiloride

The oral sensation elicited by carbonated water is reduced by capsaicin and by blockers of carbonic anhydrase. We have investigated the temporal profile of this sensation and its cross-desensitization by capsaicin. We additionally tested if the sensation is influenced by amiloride. Following pretreatment of half of the dorsal tongue with 33 p.p.m. capsaicin, carbonated water was flowed over the tongue bilaterally for 5, 15 or 60 s. Subjects then performed a two-alternative forced choice test by indicating which side of the tongue had a stronger sensation and separately rated the sensory intensity on each side. Capsaicin significantly reduced the intensity of sensation elicited by carbonated water, consistent with cross-desensitization. This effect was weaker at 60 s because of a significant decline (desensitization) in ratings of the intensity of carbonated water on both sides of the tongue. Pretreatment with amiloride resulted in a small but significant increase in the intensity of the sensation elicited by the 15 s carbonated water stimulus, suggesting an amiloride-sensitive transduction mechanism.     

Time course of self-desensitization of oral irritation by nicotine and capsaicin

Nicotine contacting mucous membranes elicits irritation that decreases with repeated exposures (self-desensitization). We investigated the time course of nicotine self-desensitization and compared it with that of capsaicin. Nicotine (300 mM, 10 microl) was applied to one-half of the dorsal tongue and vehicle to the other. Following a rest period ranging from 0.5 to 48 h, nicotine (5 microl) was reapplied to each side of the tongue and subjects indicated on which side they experienced stronger irritation and separately rated the intensity of the sensation on each side. After intervals of 0.5, 1, and 24 h, a significant majority of subjects chose the vehicle-treated side as having stronger irritation and assigned significantly higher intensity ratings to that side, indicating self-desensitization. The effect was not present after 48 h. By comparison, 10 parts per million (ppm) (33 microM) capsaicin induced significant self-desensitization at 1 but not 24 h, whereas a higher concentration of capsaicin (100 ppm, 330 microM) induced significant self-desensitization at intervals of 1, 24, and 48 h. These results indicate that initial exposure to nicotine or capsaicin can markedly attenuate irritant sensations elicited by subsequent exposure to these irritants hours to days later.     

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 chemical excitation of nociceptors in the oral cavity via the conversion of CO(2) to carbonic acid in a reaction catalyzed by carbonic anhydrase. In separate studies, we tested if the carbonic anyhdrase blocker, acetazolamide, reduced either the intensity of sensation in humans or c-fos expression by trigeminal neurons in rats, evoked by application of carbonated water to the tongue. In the psychophysical experiment, one-half of the dorsal tongue was pretreated with acetazolamide (1 or 2%), after which the tongue was exposed bilaterally to carbonated water. In a two-alternative forced-choice paradigm, subjects chose which side of the tongue yielded a stronger sensation and additionally rated the magnitude of sensation on each side. Pretreatment with acetazolamide reduced the magnitude of sensation elicited by carbonated water in a concentration-dependent manner, since a significant majority of subjects chose the untreated side of the tongue as having a stronger sensation and assigned significantly higher intensity ratings to that side. Acetazolamide did not affect the irritant sensation from citric acid, while capsaicin pretreatment reduced both the sensation elicited by carbonated water and the irritation induced by citric acid application. In a separate experiment using rats, delivery of carbonated water to the tongue significantly increased the number of cells expressing c-fos-like immunoreactivity in the dorsomedial trigeminal nucleus caudalis (versus saline controls); this was significantly reduced by pretreatment with acetazolamide. Our results support the hypothesis that carbonated water activates lingual nociceptors via conversion of CO(2) to carbonic acid; the nociceptors in turn excite trigeminal neurons involved in signaling oral irritation.     

Modulation of oral heat and cold pain by irritant chemicals

Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.     

Taste suppression following lingual capsaicin pre-treatment in humans

The effect of oral capsaicin on taste sensations in humans was reinvestigated with attention to methodological issues raised in previous studies, including the mode of presentation and temperature of the tastant stimulus, as well as the sensitizing and desensitizing properties of capsaicin. One-half of the dorsal anterior tongue was pre-treated with capsaicin, followed by bilateral tastant application (sucrose, NaCl, quinine, monosodium glutamate and citric acid). Subjects indicated on which side the taste intensity was greater in a two-alternative, forced-choice procedure and also rated taste intensity independently on each side of the tongue. Each of the five tastants was tested sequentially, with reapplication of capsaicin between trials in order to maintain a constant level of burn. Four experiments were conducted: (i) a high concentration (33 p.p.m.) (109 microM) capsaicin effect on taste intensity elicited by high tastant concentrations; (ii) a high concentration capsaicin effect on taste intensity elicited by low tastant concentrations; (iii) a low concentration (1.5 p.p.m.) (4.9 microM) capsaicin effect on taste intensity elicited by low tastant concentrations; and (iv) validation of the method for localizing taste by pre-treating one side of the tongue with Gymnema sylvestre, followed by bilateral application of sucrose. In the first experiment, a significant proportion of the subjects chose the non-treated side in the two-alternative, forced-choice procedure and assigned significantly higher ratings to that side for sucrose-induced sweetness, quinine-induced bitterness and glutamate-induced umami sensations. Salty and sour sensations were not different between sides. A 15 min break was imposed in order to allow the capsaicin burn to disappear and desensitization to set in, followed by reapplication of the tastant test solutions. There were no bilateral differences in the intensity of the sensations elicited by any of the five tastants. Similar results were obtained in experiments 2 and 3. In the fourth experiment, all 15 subjects tested chose the side not treated with Gymnema sylvestre as having a stronger sweet taste and assigned significantly higher ratings to that side, thereby validating the method for taste localization. These results indicate that oral capsaicin reduces certain but not all taste sensations and are discussed in terms of possible physiological and cognitive interactions.     

The psychophysical relationship between bitter taste and burning sensation: evidence of qualitative similarity

Although it has long been studied as a pure sensory irritant, the ability of capsaicin to evoke, mask, and desensitize bitter taste suggests that burning sensations and bitter taste might be closely related perceptually. The current study investigated the psychophysical relationship between bitterness and burning using 2 different approaches. In Experiment 1, spatial discrimination of 4 taste stimuli was measured in the presence or absence of capsaicin. The subjects' task was to report which of 3 swabs, spaced 1 cm apart and presented to the tongue tip, contained a taste stimulus when 1) water was presented on the other 2 swabs or 2) when 10 muM capsaicin was presented on all 3 swabs. The presence of capsaicin did not change performance on the 3 alternative forced-choice (3-AFC) task for sweet, sour, and salty stimuli, while the localization error for 1.8 mM quinine sulfate (QSO(4)) increased significantly. In Experiment 2, the perceptual similarity/dissimilarity of taste stimuli and capsaicin was measured directly using pairs of stimuli applied to opposite sides of the tongue tip on swabs separated by 2 cm. Multidimensional scaling analyses showed that capsaicin fell nearer to QSO(4) than to any other taste stimulus. Cluster analysis corroborated this finding: capsaicin was closely linked with QSO(4) and the capsaicin-QSO(4) group was separated from the other taste stimuli. The latter result indicated that bitterness was more similar to burning than to the other tastes. These findings imply that despite being mediated by different sensory modalities, bitterness and burn are qualitatively similar. We speculate that this similarity reflects a common function of these 2 sensations as sensory signals of potentially harmful stimuli.     

Stimulation of bitterness by capsaicin and menthol: differences between lingual areas innervated by the glossopharyngeal and chorda tympani nerves

Capsaicin is viewed as a purely chemesthetic stimulus that selectively stimulates the somatosensory system. Here we show that when applied to small areas of the tongue, capsaicin can produce a bitter taste as well as sensory irritation. In experiment 1, individuals were screened for the ability to perceive bitterness from capsaicin on the circumvallate papillae. Fifteen of 25 subjects who reported at least weak bitterness rated the intensity of taste, irritation and coolness produced by 100-320 microM capsaicin and 100-320 mM menthol applied via cotton swabs to the tip (fungiform region), the posterior edge (foliate region), and the dorsal posterior surface (circumvallate region) of the tongue. Sucrose, citric acid, sodium chloride and quinine hydrochloride were applied to the same areas to assess tastes responsiveness. On average, capsaicin and menthol produced "moderate" bitterness (and no other significant taste qualities) in the circumvallate region, and weaker bitterness on the side and tip of the tongue. Sensory irritation from capsaicin was rated significantly higher at the tongue tip, whereas menthol coolness was rated higher in the circumvallate region. In experiment 2 we applied sucrose and quinine hydrochloride together with capsaicin to investigate the effects other taste stimuli might have on capsaicin's reported bitterness. As expected, adding quinine produced stronger bitterness in the circumvallate and fungiform regions, and adding sucrose significantly reduced the bitterness of capsaicin in the circumvallate region. Overall, the results suggest that capsaicin and menthol are capable of stimulating a subset of taste neurons that respond to bitter substances, perhaps via receptor-gated ion channels like those recently found in capsaicin- and menthol-sensitive trigeminal ganglion neurons, and that the glossopharyngeal nerve may contain more such neurons than the chorda tympani nerve. That some people fail to perceive bitterness from capsaicin further implies that the incidence of capsaicin-sensitive taste neurons varies across people as well as between gustatory nerves.     

Sensory irritation and taste produced by NaCl and citric acid: effects of capsaicin desensitization

Three experiments were conducted to measure the sensory irritationproduced by two prototypical gustatory stimuli: citric acidand NaCl. The stimuli were applied to the tip of the tongueon filter paper disks. The first experiment revealed that solutionsof NaCl and citric acid that produced approximately equal tastesensations also produced similar amounts of irritation; thatthe psychophysical functions for irritation were approximatelytwice as steep as the functions for taste; and that irritationgrew over time for NaCl but not for citric acid. When viewedas a percentage of the taste sensation at 25 s, NaCl irritationaveraged 23% at the lowest concentration and 70% at the highestconcentration; citric acid irritation averaged 44% at the lowestconcentration and 98% at the highest concentration. The secondexperiment investigated whether the irritation produced by thesetwo stimuli was mediated via capsaicin-sensitive (CS) fibers.The experiment included a pre-test, an irritation treatmentwith either capsaicin (a desensitizing agent) or zingerone (anon-desensitizing agent), a 15 min rest period and a post-test.Reductions in irritation and taste occurred following treatmentwith both capsaicin and zingerone. A third experiment demonstratedthat the majority of the effect of zingerone on taste and irritationwas due to a perceptual context effect. After the context effectwas taken into account, capsaicin desensitization remained significantfor both salt taste and salt irritation at the highest concentration.A similar pattern of results for citric acid suggests that bothcitric acid and NaCl produce irritation in part via CS fibers.The results are discussed in terms of the ability of subjectsto discriminate the gustatory and chemesthetic components oforal sensations and the role of salt and acid irritation inflavor perception.     

Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction.

The activity of taste cells maintained in the intact hamster tongue was monitored in response to acid stimulation by recording action currents from taste receptor cells with an extracellular "macro" patch pipette: a glass pipette was pressed over the taste pore of fungiform papillae and perfused with citric acid, hydrochloric acid, or NaCl. Because this technique restricted stimulus application to the small surface area of the apical membranes of the taste cells, many nonspecific, and potentially detrimental, effects of acid stimulation could be avoided. Acid stimulation reliably elicited fast transient currents (action currents of average amplitude, 9 pA) which were consistently smaller than those elicited by NaCl (29 pA). The frequency of action currents elicited by acid stimuli increased in a dose-dependent manner with decreasing pH from a threshold of about pH 5.0. Acid-elicited responses were independent of K+, Na+, Cl-, or Ca2+ at physiological (salivary) concentrations, and were unaffected by anthracene-9-carboxylic acid, tetraethylammonium bromide, diisothiocyanate-stilbene-2,2'-disulfonic acid, vanadate, or Cd2+. In contrast, amiloride (< or = 30 microM) fully and reversibly suppressed acid-evoked action currents. At submaximal amiloride concentrations, the frequency and amplitude of the action currents were reduced, indicating a reduction of the taste cell apical conductance concomitant with a decrease in cell excitation. Exposure to low pH elicited, in addition to transient currents, an amiloride-sensitive sustained d.c. current. This current is apparently carried by protons instead of Na+ through amiloride-sensitive channels. When citric acid was applied while the taste bud was stimulated by NaCl, the action currents became smaller and the response resembled that produced by acid alone. Because of the strong interdependence of the acid and salt (NaCl) responses when both stimuli are applied simultaneously, and because of the similarity in the concentration dependence of amiloride block, we conclude that amiloride-sensitive Na+ channels on hamster taste receptor cells are permeable to protons and may play a role in acid (sour) taste.     

Self- and cross-desensitization of oral irritation by menthol and cinnamaldehyde (CA) via peripheral interactions at trigeminal sensory neurons

Menthol and cinnamaldehyde (CA) are plant-derived spices commonly used in oral hygiene products, chewing gum, and many other applications. However, little is known regarding their sensory interactions in the oral cavity. We used a human psychophysics approach to investigate the temporal dynamics of oral irritation elicited by sequential application of menthol and/or CA, and ratiometric calcium imaging methods to investigate activation of rat trigeminal ganglion (TG) cells by these agents. Irritancy decreased significantly with sequential oral application of menthol and CA (self-desensitization). Menthol cross-desensitized irritation elicited by CA, and vice versa, over a time course of at least 60 min. Seventeen and 19% of TG cells were activated by menthol and CA, respectively, with ～50% responding to both. TG cells exhibited significant self-desensitization to menthol applied at a 5, but not 10, min interval. They also exhibited significant self-desensitization to CA at 400 but not 200 μM. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 μM also cross-desensitized menthol-evoked responses. The results support the argument that the perceived reductions in oral irritancy and cross-interactions between menthol and CA and menthol observed (at least at short interstimulus intervals) can be largely accounted for by the properties of trigeminal sensory neurons innervating the tongue.     

Capsaicin cross-desensitization on the tongue: psychophysical evidence that oral chemical irritation is mediated by more than one sensory pathway

Psychophysical measurements were made of the perceived intensityand quality of sensations of chemical irritation before andafter the tip of the tongue had been desensitized to capsaicin(10 ppm). The results of the first experiment showed that capsaicindesensitization tended to reduce the perceived intensity ofirritation produced by approximately equipotent concentrationsof capsaicin (3 ppm), ethanol (30%), cinnamic aldehyde (2.5%)and NaCl (5M) applied to the tongue on filter paper disks; however,the reduction in irritation was less for the latter three compoundsthan for capsaicin and failed to reach statistical significancefor ethanol. Ratings of sensation quality suggested that thefour irritants produced different quality ‘profiles’,and that ethanol and cinnamic aldehyde were characterized bysensations of numbness as well as by sensations of burning andstinging/pricking. Follow-up experiments in which subjects ratedthe perceived intensity of individual sensation qualities showedthat desensitization dramatically reduced the burning and stinging/prickingcomponents of irritation, but left the sensations of numbnessand chemogenic warmth unchanged. It is concluded that lingualchemesthetic sensations are multidimensional, and mediated byboth capsaicinsensitive and capsaicin-insensitive sensory pathways.     

Effects of oral capsaicin on gustatory, olfactory and irritant sensations and flavor identification in humans who regularly or rarely consume chili pepper

We explore interactions between the irritant effects of oralcapsaicin and gustatory and olfactory sensations, and the extentto which experience with chili pepper, and liking for its sensoryproperties are associated with changes in the perception oforal capsaicin. Oral capsaicin partially masks gustatory andolfactory sensations, but surprisingly, it does not interferewith flavor identification Regular users rate the intensityof orally-induced irritation from capsaicin as markedly lowerIn spite of this difference, the partial masking of the magnitudeof olfactory or gustatory sensations exerted by capsaicin isapproximately equal in the two groups. There are indicationsthat decrements in flavor identification under capsaicin aregreater in chili dislikers (non-eaters). The pattern of resultssuggests that the masking effect of capsaicin on taste and smellarises at the stage of processing before (or on a parallel pathto) the appreciation of the magnitude of the capsaicin-inducedburn sensation.     

Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist.

Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Furthermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent.     

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

Experiments carried out in conscious guinea pigs suggest that citric acid-evoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicin-sensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicin-insensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low Cl- buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 microM capsazepine, Ca2+-free perfusate, 0.1 microM iberiotoxin, 1 microM atropine, 10 microM isoproterenol, 10 microM albuterol, 3 microM indomethacin, 0.1 microM HOE-140, a combination of neurokinin1 (NK1; CP-99994), NK2 (SR-48968), and NK3 (SB-223412) receptor antagonists (0.1 microM each), a combination of histamine H1 (3 microM pyrilamine) and cysLT1 (1 microM ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels.     

Anterior Tongue Stiomulation with Amiloride Suppresses NaCl Saltiness, but not Citric Acid Sourness in Humans

Suppression of the saltiness of NaCI solutions by amiloride,a sodium channel blocker, has previously been reported a numberof times in humans. This suppression was seen with techniquesthat involved stimulation of small areas of the tongue. It wasnot certain, however, whether amiloride would suppress saltinesswith stimulation of a much larger area of the tongue; one publishedstudy, in fact, found negative results with whole mouth stimulation.For this study, eight subjects dipped a large part of the anteriorportion of the tongue into a 10-ml sample of NaCI solution,or a NaCI and amiloride solution, and reported its magnitudeof saltiness intensity. The results show that amiloride suppressedthe saltiness of NaCI when a large area of the anterior tonguewas stimulated. Consistent with previous studies, there wasindividual variability across subjects in this suppressive effectof amiloride. This study also used this method to test the effectsof amiloride on the sourness of citric acid, which was not expectedto be affected. No suppression of sourness was seen with amiloride.Chem. Senses 21: 113–120, 1996.     

Interactions between oral chemical irritation, taste and temperature

The oral chemical irritant, capsaicin, at 2, 4 and 8 p.p.m.,was combined in mixtures with sucrose (Experiment 1), sodiumchloride (Experiment 2) and soup (Experiment 3), each evaluatedat two temperatures. These mixtures were rated for their sweetnessand/or saltiness, intensity of burning sensation and total mixtureintensity. In both solution and soup, sweetness was suppressed,whereas saltiness showed only minor suppression in low NaCl,high capsaicin mixtures. The burning sensation produced by capsaicinwas uninfluenced by sucrose, while NaCl increased the burningsensation. Total mixture intensity was entirely determined bycapsaicin concentration in mixtures with sucrose, although NaClcontributed in NaCl/capsaicin mixtures. Varying temperatureinfluenced the burning sensation and total intensity of sucrose/capsaicinmixtures, but did not modulate the effects of capsaicin on taste.Explanations of taste suppression in terms of cognitive andstructural models are examined. The differential effect of capsaicinon sweetness and saltiness is also considered in terms of theirritant properties of NaCl.     

Sensitization and desensitization to allyl isothiocyanate (mustard oil) in the nasal cavity

The aim of this study was to investigate the response, acute effects and time-course of sensitization and desensitization to allyl isothiocyanate (mustard oil) nasal stimuli in healthy subjects. Sixty subjects participated in the experiment, which employed psychophysical (intensity ratings) and psychophysiological (skin conductance response) measurements. Nasal stimuli were delivered three times with different inter-stimulus intervals. The results showed that the psychophysical and psycho-physiological data were correlated and that the successive nasal stimuli after a short period of time (<2 min) produced increased intensity of irritation, whereas the stimuli delivered after >3 min produced a markedly decreased intensity of irritation. These findings are in agreement with those obtained with capsaicin, the most frequently used irritant molecule.