Chem. Senses 27: 353-365,
2002
© Oxford University Press 2002
Taste Suppression Following Lingual Capsaicin Pre-treatment in Humans
1 Section of Neurobiology, Physiology and Behavior, University of California, 1 Shields Avenue, Davis, CA 95616, USA 2 Department of Food Science and Technology, University of California, 1 Shields Avenue, Davis, CA 95616, USA
Correspondence to be sent to: E. Carstens, Section of Neurobiology, Physiology and Behavior, University of California, 1 Shields Avenue, Davis, CA 95616, USA. e-mail: eecarstens{at}ucdavis.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
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 µM) 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 µM) 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.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Capsaicin, which is the pungent principle of chilli peppers, elicits an irritant sensation by binding to `capsaicin' (VR-1) receptors that are also gated by noxious heat and acidic stimuli (Caterina et al., 1997
; Tominaga et
al., 1998). VR-1 receptors are expressed in the endings of
trigeminal nociceptors that innervate the oral mucosa
(Sostman and Simon, 1991;
Bryant and Moore, 1995;
Liu and Simon, 1996;
Liu et al., 2000),
afferent fibres of which project to the brainstem trigeminal complex (Carstens
et al., 1995,
1998). Chemicals eliciting
taste, on the other hand, evoke activity in taste receptor cells, which in
turn activate primary gustatory neurons of the chorda tympani,
glossopharyngeal and/or vagus nerves that project to the rostral aspect of the
nucleus of the solitary tract (Hamilton
and Norgren, 1984; Scott
et al., 1986; Travers
et al., 1986;
McPheeters et al.,
1990; Nakamura and Norgren,
1991; Travers and Norgren,
1995; Di Lorenzo and Lemon,
2000; Smith et al.,
2000). Although the trigeminal and gustatory pathways are
anatomically distinct, the significant overlap of receptive fields and the
convergence of lingual somatosensory and gustatory information within the
brainstem (Ogawa et al.,
1984,
1988;
Hayama et al., 1985;
Sweazey and Bradley, 1988;
Travers and Norgren, 1995),
thalamus (Nomura and Ogawa,
1985; Pritchard et al.,
1986,
1989;
Lenz et al., 1997)
and cortex (Yamamoto, 1984;
Cerf-Ducastel et al.,
2001) provide substrates for possible interactions.
Anecdotal evidence suggests that oral irritants may alter the perceptions
of taste elicited by various foods. Infrequent consumers of spicy food often
complain that irritant chemicals make it difficult to taste food, whereas
frequent consumers suggest that taste sensations are enhanced by the presence
of these same chemicals (Lawless et
al., 1985). In controlled psychophysical studies,
pre-treating the oral cavity with capsaicin had no reported effect on the
recognition thresholds of gustatory stimuli
(Szolcsányi, 1977). In
other studies the perception of suprathreshold taste sensations appeared to be
modified (Lawless and Stevens,
1984; Lawless et al.,
1985; Cowart, 1987;
Prescott et al.,
1993; Prescott and Stevenson,
1995; Stevenson and Prescott,
1997). There is a general consensus that capsaicin reduces
perceived sweet intensity. However, its effect on other taste qualities
varies. Indeed, it appears that the method of capsaicin/tastant delivery
(pre-treatment versus mixture) influences the degree to which any effects are
observed (Cowart, 1987).
Several methodological concerns are worthy of special attention. Repeated
application of capsaicin at short interstimulus intervals results in an
increase in the perceived burn intensity
(Stevens and Lawless, 1987;
Cliff and Green, 1996;
Dessirier et al.,
1997; Prescott and
Swain-Campbell, 2000), a phenomenon now termed sensitization. In
contrast, if capsaicin is reapplied following a longer inter-stimulus interval
(>2.5-5 min), the perceived irritation is markedly reduced, resulting in a
state of desensitization
(Szolcsányi, 1977;
Geppetti et al.,
1993; Cliff and Green,
1996; Green, 1998;
Green and Rentmeister-Bryant,
1998; Prescott and
Swain-Campbell, 2000), which can eventually be overcome by
reapplying the capsaicin at shorter inter-stimulus intervals (stimulus-induced
recovery) (Green, 1998;
Green and Rentmeister-Bryant,
1998). It is therefore important to control for the inherent
sensitizing and desensitizing properties of capsaicin when assessing its
effect on taste.
Second, cooling can reduce or eliminate the irritant effects elicited by
capsaicin. An earlier study found a modest decrement in the burn intensity of
capsaicin solutions presented at 21°C as compared to 37°C
(Prescott et al.,
1993). Interestingly, varying the temperature did not modulate the
effects of capsaicin on taste when the irritant was presented in a mixture
with sucrose or NaCl. However, as indicated by those authors, this lack of
effect may have been due to temporal factors associated with how the cooling
was administered (i.e. administration of a cooled capsaicin—tastant
mixture versus cooling a pre-existing burn).
The present study was undertaken in order to re-evaluate the effect of
pre-treating the lingual epithelium with capsaicin while controlling for any
possible confounding effects of capsaicin sensitization/desensitization or
cooling by tastant administration. Moreover, we employed the very sensitive
half-tongue, two-alternative, forced-choice protocol coupled with bilateral
intensity ratings that we have used previously for studying oral irritation
(Dessirier et al.,
1998,
1999;
Simons et al.,
1999).
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
General procedures
Subjects
A total of 107 healthy volunteers aged from 18 to 63 years volunteered to
participate in the experiments. All were either students or staff at the
University of California, Davis. The subjects were divided into three
approximately equal groups, with a fourth group of 15 subjects used in
experiment 4. Each group participated in a single experiment (experiment 1, 2,
3 or 4) (see below) lasting 
45 min (except for experiment 4 which lasted
10 min). The subjects were asked to refrain from eating, drinking or
smoking for at least 1 h prior to their scheduled session (12 subjects
reported being smokers). Moreover, the subjects were asked to avoid eating
anything spicy for at least 2 days prior to the experiment and these criteria
were verified by interview. The University of California, Davis Human Subjects
Review committee approved the experimental protocol.
Chemical stimuli
The oral irritant capsaicin (Sigma, St Louis, MO) was used at a
concentration eliciting a burn of moderate intensity (109 µM) in
experiments 1 and 2 or of low intensity (4.9 µM) in experiment 3. KCl
(Mallinkrodt, Paris, KY) was used at a concentration of 250 mM (experiments 1
and 2) or 100 mM (experiment 3) as a distractor/control (see below). A series
of five tastant test solutions (sucrose, NaCl, citric acid, quinine and
monosodium glutamate) that were approximately matched in intensity were used
in each experiment. The tastant concentrations are given for each experiment
under the section on specific procedures. All chemicals were of reagent grade
and dissolved in distilled water except for capsaicin, which was dissolved
initially as a stock solution of 3.3 mM in a solution containing 50% ethanol.
Working capsaicin concentrations contained 1.65% and 0.075% ethanol, which is
well below the level needed for eliciting activity in rat trigeminal
nocieptive neurons (Carstens et
al., 1998).
Experiment 4 was a control experiment for ensuring that the subjects could detect lateral differences in taste intensity. The chemicals used and their concentrations are given in the section on specific procedures.
Stimulus application
Prior to the start of each experiment, the subjects familiarized themselves
with the quality and intensity of each of the tastant test solutions. All
subjects reported that the tastant solutions were suprathreshold. Capsaicin's
effect on taste perception was then tested using the same half-tongue,
two-alternative, forced-choice procedure we have used previously (Dessirier
et al., 1998,
1999;
Simons et al., 1999).
Capsaicin was applied unilaterally to the anterior half of the dorsal lingual
surface using a cotton-tipped applicator. The side of the tongue receiving
capsaicin was counter-balanced across the subjects. It has been shown
previously that subjects often have the expectation that spices decrease
perceived taste (Stevenson and Prescott,
1997). In order to counter this potential bias, we applied KCl
(250 or 100 mM) in a similar manner to the opposite side of the tongue as a
distractor/control. The subjects were instructed that two spicy chemicals were
going to be painted on their tongues, one of which had a pungent quality but
no taste (capsaicin) and the other of which had a taste but no pungency (KCl).
Following this, the subjects were instructed to rinse with warm water
(37°C) in order to remove any residual capsaicin and KCl from their
tongues. It also had the effect of eliminating taste adaptation effects that
might have been elicited by the KCl. Immediately after the rinse, the subjects
were required to attend to the burning sensation produced by the capsaicin and
rate the intensity using a 0-10 point intensity scale (0 = no sensation and 10
= strongest sensation imaginable). The subjects were then given a small
plastic cup containing 5 ml of one of the five tastant test solutions warmed
to 37°C, instructed to place the solution in the anterior half of the
buccal cavity and choose the side of their tongues having the strongest taste
sensation. In addition, the subjects were asked to provide bilateral ratings
of taste intensity using the same 0-10 point intensity scale. In an effort to
prevent the subjects from combining sensations of taste and irritation, they
were asked to ignore the burning sensation and focus exclusively on the taste
of the tastant solution. After expectoration of the tastant test solution, the
subjects rinsed their mouths with warmed distilled water in order to remove
the tastant and avoid cross-adaptation effects in subsequent taste stimuli and
rated the intensity of the residual burn left on their tongues. If the
intensity rating decreased by >2 points from its original intensity,
capsaicin and KCl were reapplied until the level of irritation on the
capsaicin-treated side was once again equal to its original level. This
procedure was followed by a rinse, as before, in order to remove any residual
KCl taste that may have confounded the results. The subjects were then given
the second tastant test solution and the procedure was repeated. This
procedure was repeated successively for each of the five tastant solutions.
The order of presentation of the tastants was randomized across the
subjects.
In order to evaluate the effect of capsaicin desensitization on taste
perception, the subjects were asked to rinse three times with distilled water
and wait a minimum of 15 min or until the burn from the previous capsaicin
application(s) had completely dissipated. When the rest period concluded,
sequential application of the tastant series was repeated in the absence of
any oral irritation, with the subjects performing the two-alternative,
forced-choice procedure and giving bilateral intensity ratings as described
above. The tastant test solutions were presented in a randomized order and the
subjects rinsed with warmed (37°C) distilled water between tastants. At
the conclusion of the session, capsaicin desensitization was verified as
follows. Two filter papers (1 cm diameter) (Whatman International Ltd,
Maidstone, UK) were saturated with 20 µl of the same capsaicin solution
applied previously to the tongue and placed with forceps onto each side of the
tongue in the areas previously treated with capsaicin or KCl. After 10 s
during which the mouth was held closed, the filter papers were removed and, in
a two-alternative, forced-choice procedure, the subjects chose the side of the
tongue having the stronger burning sensation.
The procedure used for stimulus application in experiment 4 is given in the section on specific procedures.
Data analysis
A binomial analysis was used for determining whether a significant majority
of the subjects chose the control (KCl-pre-treated) side of the tongue as
having a stronger taste sensation. In addition, a d' analysis
(Ennis, 1993) was performed in
order to measure the strength and significance of the effect using a
previously used method (Bi and O'Mahony,
1995). Significant differences in the mean taste intensity ratings
for each side of the tongue were assessed using Student's paired
t-tests with a Bonferroni correction. One-way analysis of variance
(ANOVA) was used for determining whether significant differences existed in
the mean level of irritation experienced by the subjects during each of the
tastant evaluations. All data are presented as means ± SE. A
significance level of P < 0.05 was taken as significant for the
binomial analysis and the ANOVA, whereas a significance level of P
< 0.01 was used in the Bonferroni-corrected t-tests.
Specific procedures
Experiment 1
Thirty-one subjects (11 male and 20 female) ranging from 18 to 43 years in
age participated in experiment 1. This experiment tested the effect of
unilateral application of the high capsaicin concentration (109 µM, with
250 mM KCl applied to the opposite side) on taste that was elicited by high
concentrations of each tastant: sucrose (300 mM) (Mallinkrodt, Paris, KY),
NaCl (300 mM) (Fisher Scientific, Fair Lawn, NJ), citric acid (5.6 mM)
(Mallinkrodt, Paris, KY), quinine HCl (0.1 mM) (BDH Chemicals, Poole, UK) and
monosodium glutamate (30 mM) (Sigma, St Louis, MO). All aspects of the
experiment were carried out as described under the section on general
procedures.
Experiment 2
Thirty-two subjects (eight male and 24 female) ranging from 18 to 42 years
in age participated in experiment 2. This experiment tested the effect of
unilateral application of the high capsaicin concentration (109 µM
capsaicin, with 250 mM KCl applied to the opposite side) on taste that was
elicited by the low tastant concentrations (50 mM sucrose, 40 mM NaCl, 0.93 mM
citric acid, 0.01 mM quinine HCl and 10 mM monosodium glutamate). All other
aspects of the experiment were identical to those described in the section on
general procedures.
Experiment 3
Twenty-nine subjects (nine male and 20 female), 18-57 years old,
participated in experiment 3. This experiment tested the effect of the low
capsaicin concentration (4.9 µM, with 100 mM KCl applied to the opposite
side) on taste that was elicited by low tastant concentrations (50 mM sucrose,
40 mM NaCl, 0.93 mM citric acid, 0.01 mM quinine HCl and 10 mM monosodium
glutamate). All other procedures were identical to those described in the
section on general procedures.
Experiment 4: validation of the method for taste
This experiment was conducted in order to show that the present
half-tongue, two-alternative, forced-choice procedure can detect lateral
differences in taste intensity. Fifteen healthy volunteers (25-63 years of
age) were tested. Gymnema sylvestre (5% in dH2O) (Natrol, Inc.,
Chatsworth, CA) was painted onto one-half of the dorsal lingual surface using
a cotton-tipped applicator. Quinine HCl (10 mM) approximately matched in terms
of bitter taste intensity was painted onto the opposite side as a control. The
subjects rinsed their mouths with distilled water and were asked to sip 5 ml
of a 300 mM sucrose solution into the anterior portion of their mouth and
assess the sweetness on both sides of the tongue. As in the other experiments,
the subjects indicated which side of the tongue had the strongest sweet
sensation in the two-alternative, forced-choice procedure. In addition, the
subjects gave bilateral intensity ratings for the sweetness using a 0-10 scale
(0 = no sensation and 10 = strongest sensation imaginable).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Experiment 1
One goal of this experiment was to ensure that the level of irritation experienced during each of the five tastant evaluations was maintained at a constant level. In this regard, the mean intensity of the irritation induced by 109 µM capsaicin did not differ significantly (P = 0.976) when assessed prior to the application of each of the five tastants. However, capsaicin pre-treatment differentially affected the perceived taste intensities elicited by the higher tastant concentrations (Figure 1). A significant majority of the subjects chose the control side of the tongue as having the stronger taste sensation (26 out of 31) (P < 0.001) for sucrose-induced sweetness, giving a significant d' value of 1.4 (P < 0.001). Consistent with this, significantly lower intensity ratings were assigned to the capsaicin-treated side as compared to the control side (4.2 ± 0.4 versus 5.6 ± 0.3) (P < 0.001) (Figure 1A). A significant majority of the subjects also chose the control side of the tongue as having the stronger bitter taste for quinine-induced bitterness (22 out of 31) (P = 0.028) (equivalent to a d' value of 0.78). However, the bilateral intensity ratings were not significantly different although there was a trend towards higher ratings on the control side (3.4 ± 0.4 versus 4.0 ± 0.4) (P = 0.079) (Figure 1B). Our interpretation is that the subjects reliably perceived an intensity difference in the two-alternative, forced-choice procedure, but that this difference was too small to detect by the scaling method. In contrast to sweetness and bitterness the subjects did not consistently choose the control side as having a stronger intensity for NaCl-induced saltiness (18 out of 31) (P = 0.473) (equivalent to a d' value of 0.29) (P = 0.473), citric acid-induced sourness (13 out of 31) (P = 0.537) (equivalent to a d' value of 0.29) (P = 0.537) and monosodium glutamate-induced umami (18 out of 31) (P = 0.473) (equivalent to a d' value of 0.29) (P = 0.473) in the two-alternative, forced-choice procedure, nor was there a significant bilateral intensity difference for saltiness (4.7 ± 0.4 versus 4.9 ± 0.4 respectively) (P = 0.691) (Figure 1C), sourness (3.5 ± 0.4 versus 3.3 ± 0.4 respectively) (P = 0.531) (Figure 1D) or umami (4.3 ± 0.3 versus 4.7 ± 0.4 respectively) (P = 0.353) (Figure 1E).
|
After the capsaicin burn had dissipated and desensitization had set in, the subjects sampled the five tastant test solutions again. During this period the subjects did not consistently choose either side of the tongue as having the stronger taste sensation in the two-alternative, forced-choice procedure, nor were there any significant laterality differences in the intensity ratings for any of the tastants (Figure 2A-E). Desensitization by the prior capsaicin applications was verified. One hundred percent of the subjects chose the control side as having the stronger irritant sensation when capsaicin was reapplied at the end of the session (31 out of 31) (P < 0.001) and gave significantly higher ratings to the control side as compared to the desensitized side (5.8 versus 2.8) (P < 0.001).
|
Experiment 2
As predicted by Weber's Law, we hypothesized that the taste suppression effect of capsaicin would be more obvious if the intensity of the various tastant test solutions were minimized. Therefore, the concentrations of the tastant test solutions in experiment 2 were just above recognition thresholds. As in experiment 1, the level of perceived irritation remained constant during each of the five tastant evaluation periods (P = 0.644). Moreover, as with the higher tastant concentrations, a significant majority of the subjects chose the control side of the tongue as having the stronger taste sensation for sucrose-induced sweetness (28 out of 32) (P < 0.001) and quinine-induced bitterness (26 out of 32) (P < 0.001). The equivalent d' values (1.63 and 1.25 respectively) were also significant (P < 0.001 respectively). In addition, a significant majority of the subjects chose the control side as having a stronger monosodium glutamate-induced umami taste (24 out of 32) (P = 0.008) giving a significant (P = 0.008) d' value of 0.95. In accordance with these findings, significant differences in the bilateral intensity ratings were found for sweetness (3.3 ± 0.3 versus 4.6 ± 0.4 respectively) (P = 0.001) (Figure 3A) and bitterness (3.3 ± 0.4 versus 4.3 ± 0.4 respectively) (P = 0.009) (Figure 3B). Although approaching significance, the bilateral intensity ratings for monosodium glutamate-induced umami were not statistically different (3.6 ± 0.3 versus 4.6 ± 0.3 respectively) (P = 0.015) (Figure 3E) again suggesting that data derived from paired comparisons are more sensitive to small discriminatory differences than those obtained from scaling. The subjects did not consistently choose either side as having the stronger taste for NaCl-induced saltiness (20 out of 32) (P = 0.215) or citric acid-induced sourness (19 out of 32) (P = 0.377), nor were the bilateral intensity ratings significantly different for saltiness (2.9 ± 0.4 versus 3.4 ± 0.4 respectively) (P = 0.081) (Figure 3C) or sourness (3.8 ± 0.4 versus 4.2 ± 0.3 respectively) (P = 0.531) (Figure 3D).
|
When the subjects were retested after the capsaicin burn had subsided they did not consistently choose either side the tongue in the two-alternative, forced-choice procedure, nor were there any significant laterality differences in the intensity ratings for any of the tastants (Figure 4A-E). As in experiment 1, all of the subjects (32 out of 32) (P < 0.001) were desensitized to capsaicin as determined in the two-alternative, forced-choice procedure and gave significantly (P < 0.001) lower ratings to the capsaicin pre-treated side (2.2) as opposed to the control side (5.9).
|
Experiment 3
In order to minimize any potential confounding effects of masking, a lower concentration of capsaicin (4.9 µM), which elicited a very weak burning sensation, was used in conjunction with low tastant concentrations. The level of perceived irritation remained constant during each of the five tastant evaluation periods (P = 0.936). As in experiments 1 and 2, a significant majority of the subjects chose the control side of the tongue as having the stronger sensation of sucrose-induced sweetness (22 out of 29) (P = 0.008) and monosodium glutamate-induced umami (21 out of 29) (P = 0.024). The corresponding d' values (0.990 and 0.840 respectively) were also significant (P = 0.008 and 0.024 respectively). The intensity ratings for sucrose-induced sweetness were consistent as significantly higher ratings were given to the untreated side of the tongue (3.1 ± 0.3 versus 2.3 ± 0.4) (P = 0.011) (Figure 5A). The intensity difference for monosodium glutamate-induced umami failed to reach a significant level (2.8 ± 0.3 versus 2.2 ± 0.3) (P = 0.048) (Figure 5E), although there was a trend for higher ratings on the untreated side. Neither side of the tongue was consistently selected as having the stronger sensation for all the other tastant test solutions, nor were there any differences in the intensity ratings assigned to each side (Figure 5B-D).
|
The subjects did not consistently choose either side of the tongue as having the stronger taste sensation during the period of capsaicin desensitization, nor were there any significant laterality differences in the intensity ratings for any of the tastants (Figure 6A—E). Capsaicin desensitization was verified in 86% of the subjects that chose the control side as having the stronger irritant sensation when capsaicin was reapplied at the end of the session (25 out of 29) (P < 0.001). As expected, the mean burn rating for the control side of the tongue was significantly higher than the mean rating for the capsaicin-desensitized side (2.4 versus 4.1 respectively) (P < 0.001). The data from the four subjects not desensitized were excluded from this analysis.
|
Experiment 4: validation of the method for taste
Fifteen out of 15 subjects (P < 0.001) chose the side of the tongue not receiving Gymnema sylvestre as being sweeter when evaluating the sweetness of a 300 mM sucrose solution. In addition, the ratings of sweetness were significantly higher (P < 0.001) on the quinine-treated side of the tongue as compared to those on the Gymnema sylvestre-treated side (4.1 ± 0.5 versus 1.8 ± 0.4 respectively).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
The results obtained in the present study confirm the suppressive effects of capsaicin on certain gustatory qualities, as reported previously (Lawless and Stevens, 1984
;
Lawless et al., 1985;
Cowart, 1987;
Prescott et al.,
1993; Prescott and Stevenson,
1995; Stevenson and Prescott,
1997). Whereas most prior studies have reported a suppressive
effect on sucrose-induced sweetness, the effects on other taste qualities were
inconsistent. These findings are discussed in terms of the methodology as well
as underlying psychological and physiological mechanisms. Methodological issues
The present study employed a novel half-tongue, two-alternative,
forced-choice procedure in which the subjects were asked to compare taste
sensations bilaterally following unilateral capsaicin application. This
requires that normal subjects are capable of localizing tastes within the oral
cavity. Clinical evidence indicates that patients with unilateral damage to
the chorda tympani may be unaware of the resultant taste deficit
(Kveton and Bartoshuk, 1994).
Moreover, normal subjects with unilateral local anaesthesia of the chorda
tympani mislocalize tastes to the anaesthetized side
(Lehman et al., 1995;
Yanagisawa et al.,
1998), possibly with the aid of tactile cues (`tactile capture')
(Todrank and Bartoshuk, 1991).
However, recent psychophysical data have indicated that normal subjects are
capable of localizing tastes on the tongue under controlled conditions
(Delwiche et al.,
2000; Shikata et al.,
2000; McMahon et al.,
2001). In order to ensure that our method was appropriate for
assessing laterality differences in taste intensity, we made the subjects rate
the intensity of sweetness elicited by sucrose after one side of the tongue
had been treated with Gymnema sylvestre, which blocks sweet taste transduction
(Warren et al.,
1969). The other control side was pre-treated with quinine matched
approximately to the bitterness of the Gymnema sylvestre. That all of the
subjects chose the control side as having a stronger sweet sensation supports
our contention that the half-tongue, two-alternative, forced-choice method is
appropriate for assessing bilateral taste intensity differences.
As noted in the Introduction, we attempted to control for a variety of
methodological nuances that may underlie some of the reported differences
regarding the effect of oral capsaicin on taste, including the mode of
stimulus presentation, the temperature of the stimuli at presentation and the
presence of capsaicin sensitization and/or desensitization. Since our pilot
studies indicated that the capsaicin effects were likely to be small, we
maximized the probability of discriminating small differences by using a
paradigm in which we pre-treated the dorsal lingual surface with capsaicin
followed by tastant rinses, as opposed to making the subjects assess the taste
intensity of a mixture containing both the irritant and the tastant. In a
direct comparison of these two paradigms, the former method was shown to
result in a greater apparent reduction in taste intensities
(Cowart, 1987). All solutions
were presented at 37°C in order to obviate any effect of temperature. In
addition, capsaicin was reapplied as necessary in order to maintain a constant
level of burn throughout each tastant evaluation. Finally, we employed a
strategy using difference tests coupled with intensity ratings. Difference
tests are more sensitive in detecting small differences in sensory intensity
compared to scaling procedures alone (Kim
et al., 1998), the latter having their sensitivity
reduced by boundary variance. Another advantage of our present strategy is
that the subjects compared the treated and untreated sides of the tongue
simultaneously rather than sequentially as is done in traditional `sip and
spit' techniques. This allowed the subjects to make direct sensory comparisons
that were devoid of any confounding memory effects.
We found that sucrose-induced sweetness and quinine-induced bitterness were
suppressed when the tongue was pre-treated with a relatively high capsaicin
concentration. Interestingly, the magnitude of the suppression of the
sweetness and bitterness was larger, with significant suppression of umami in
the two-alternative, forced-choice procedure when the tastant concentrations
were lowered to near-threshold levels (experiment 2). This result is
consistent with Weber's Law which predicts that, for a given absolute sensory
intensity difference between the two sides of the tongue, the fractional
difference is greater (and, hence, more easily detectable) for low than high
baseline intensities. The inhibitory effect of capsaicin on sweetness and
bitterness is consistent with previous findings showing a modest
(Lawless and Stevens, 1984) to
substantial reduction in sweetness following a capsaicin rinse
(Lawless et al.,
1985; Prescott et
al., 1993; Prescott and
Stevenson, 1995; Stevenson and
Prescott, 1997) as well as a reduction in bitterness ratings
following either a capsaicin (Lawless,
1984; Cowart, 1987)
or piperine (Lawless and Stevens,
1984) pre-rinse. The capsaicin suppression (in the
two-alternative, forced-choice procedure) of umami taste at the low monosodium
glutamate concentration was unique to the present report.
If a hiatus of >2.5-5 min is imposed following an oral capsaicin
stimulus subsequent application of capsaicin elicits a burn of substantially
reduced intensity, a phenomenon that is called desensitization
(Szolcsányi, 1977;
Green, 1989,
1998;
Geppetti et al.,
1993; Cliff and Green,
1996; Green and
Rentmeister-Bryant, 1998;
Prescott and Swain-Campbell,
2000). Previous studies have shown that quinine-and
propylthiouracil-induced bitterness
(Karrer and Bartoshuk, 1995)
as well saltiness and sourness sensations induced by high NaCl or citric acid
concentrations (Gilmore and Green,
1993) are reduced when given > 15 min after pre-treatment with
capsaicin. In the present study we did not find bilateral intensity
differences for any tastant when it was applied during the period of capsaicin
desensitization after the burn had subsided. However, our data are not
inconsistent with previous studies. In an earlier study
(Gilmore and Green, 1993),
capsaicin at a concentration (10 p.p.m.) intermediate between those used in
the present study (1.5 and 33 p.p.m.) had no effect on the salty or sour
sensations evoked by low or moderate concentrations of NaCl or citric acid
similar to those used in this study. In another earlier study
(Karrer and Bartoshuk, 1995)
desensitization by an intermediate concentration of capsaicin (10 p.p.m.) had
no effect on taste intensity, consistent with our present findings. Capsaicin
suppression of taste was only observed following desensitization by a much
higher (100 p.p.m.) concentration of capsaicin
(Karrer and Bartoshuk, 1995).
While this probably accounts for the different results with capsaicin
desensitization, there were also substantial methodological differences. The
latter study (Karrer and Bartoshuk,
1995) tracked the effects of capsaicin on taste over a period of
days, requiring the subjects to remember prior intensity ratings. This differs
markedly from the present study in which the subjects rated the tastants
15 min following capsaicin application in a two-alternative,
forced-choice paradigm that did not require memory of prior ratings.
Mechanisms of differential taste suppression
The differential effects of capsaicin on various taste qualities may have
cognitive and/or physiological underpinnings. A potential cognitive effect
might result from the dominant burning sensation drawing attention away from
the gustatory sensations, thereby resulting in lower perceived intensity
scores. A strong argument against this is our observation that only sweet,
bitter and umami taste qualities were affected while salty and sour taste
qualities were not. Moreover, capsaicin suppression of sweetness but not
strawberry flavour was demonstrated in a direct test of this hypothesis
(Prescott and Stevenson,
1995), thereby suggesting that distraction does not adequately
describe capsaicin's effect on gustatory responses.
Peripherally capsaicin application can lead to localized areas of oedema of
the tongue by its documented ability to elicit plasma extravasation
(Bryant and Moore, 1995;
Holzer, 1998). Localized
oedema could lead to closure of the taste pore thereby making it difficult for
tastant molecules to access their receptors. However, such a non-specific
mechanism should apply to all tastes and not just sweet, bitter and umami
tates. Neural mechanisms may also contribute to the selective suppressive
effect of capsaicin. Activation of the lingual nerve electrically
(Wang et al., 1995)
or chemically with capsaicin (Osada et
al., 1997) led to a reduction in NaCl-evoked responses
recorded in the rat chorda tympani. A peripheral mechanism was proposed for
explaining these findings whereby substance P released from nociceptive
terminals of the lingual nerve alters the sensitivity of taste receptor cells
(Wang et al., 1995;
Osada et al., 1997)
which express substance P (NK-1) receptors
(Chang et al., 1996).
Capsaicin was recently found to activate second messenger systems that inhibit
voltage-gated Na+ ion channels in trigeminal ganglion cells
(Liu et al., 2001),
as well as voltage-gated K+ channels in taste receptor cells (S.A.
Simon, personal communication). Given the present findings that capsaicin
selectively affected sweet, bitter and umami tastes, it is enticing to
speculate that capsaicin might affect G-protein-coupled transduction
mechanisms that have been demonstrated for these tastants
(Gilbertson et al.,
2000) while ionotropic transduction mechanisms for bitter
(quinine) and glutamate tastants
(Gilbertson et al.,
2000) might contribute to residual taste sensitivity.
Finally, a central neural effect is also possible whereby capsaicin activation of the trigeminal system modulates gustatory processing at some stage in the taste pathway such as the NTS, thalamus or cortex. Capsaicin modulation of taste could conceivably involve both peripheral and central neural interactions.
In summary, the present study showed a significant suppression of sweetness, bitterness and umami sensations following pre-treatment of the lingual epithelium with capsaicin. The suppression apparently requires the presence of an active irritant sensation, as the suppressive effect was not observed after the burn dissipated. Additional studies are needed in order to delineate the mechanisms responsible for the observed suppressive effect.
|
Acknowledgments |
|---|
The authors would like to thank Dr Benoit Rousseau for assistance in calculating the d' values. This research was supported by grants from the California Tobacco-Related Disease Research Program (nos 6RT-0231 and 10DT-0197) and the NIH (National Institute of Dental and Craniofacial Research) (no. DR13685).
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Bi, J. and O'Mahony, M. (1995) Tables for testing the significance of R-index. J. Sensory Studies, 10,341 -347.
Bryant, B.P. and Moore, P.A. (1995)
Factors affecting the sensitivity of the lingual trigeminal nerve to
acids. Am. J. Physiol., 268,R58
-R65.
Carstens, E., Saxe, I. and Ralph, R. (1995) Brainstem neurons expressing c-Fos immunoreactivity following irritant chemical stimulation of the rat's tongue.Neuroscience , 69,939 -953.[ISI][Medline]
Carstens, E., Kuenzler, N. and Handwerker, H.O.
(1998) Activation of neurons in rat trigeminal subnucleus
caudalis by different irritant chemicals applied to oral or ocular
mucosa. J. Neurophysiol., 80,465
-492.
Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D. and Julius, D. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway.Nature , 389,816 -824.[Medline]
Cerf-Ducastel, B., Van de Moortele, P.F., MacLeod, P., Le Bihan,
D. and Faurion, A. (2001) Interaction of gustatory
and lingual somatosensory perceptions at the cortical level in the human: a
functional magnetic resonance imaging study. Chem. Senses,26
, 371-383.
Chang, G.Q., Vigna, S.R. and Simon, S.A. (1996) Localization of substance P NK-1 receptors in rat tongue. Regulat. Peptides, 63,85 -89.[ISI][Medline]
Cliff, M.A. and Green, B.G. (1996) Sensitization and desensitization to capsaicin and menthol in the oral cavity: interactions and individual differences. Physiol. Behav., 59,487 -494.[Medline]
Cowart, B.J. (1987) Oral chemical
irritation: does it reduce perceived taste intensity? Chem.
Senses, 12,467
-479.
Delwiche, J.F., Lera, M.F. and Breslin, P.A.
(2000) Selective removal of a target stimulus localized by
taste in humans. Chem. Senses, 25,181
-187.
Dessirier, J.M., O'Mahony, M. and Carstens, E.
(1997) Oral irritant effects of nicotine: psychophysical
evidence for decreased sensation following repeated application and lack of
cross-desensitization to capsaicin. Chem. Senses,22
, 483-492.
Dessirier, J.M., O'Mahony, M., Sieffermann, J.M. and Carstens, E. (1998) Mecamylamine inhibits nicotine but not capsaicin irritation on the tongue: psychophysical evidence that nicotine and capsaicin activate separate molecular receptors. Neurosci. Lett., 240,65 -68.[ISI][Medline]
Dessirier, J.M., Nguyen, N., Sieffermann, J.M., Carstens, E.
and O'Mahony, M. (1999) Oral irritant properties of
piperine and nicotine: psychophysical evidence for asymmetrical
desensitization effects. Chem. Senses,24
, 405-413.
Di Lorenzo, P.M. and Lemon, C.H. (2000) The neural code for taste in the nucleus of the solitary tract of the rat: effects of adaptation. Brain Res.,852 , 383-397.[ISI][Medline]
Ennis, D.M. (1993) The power of sensory discrimination methods. J. Sens. Stud.,8 , 353-370.
Geppetti, P., Tramontana, M., Del Bianco, E. and Fusco, B.M. (1993) Capsaicin-desensitization to the human nasal mucosa selectively reduces pain evoked by citric acid. Br. J. Clin. Pharmacol., 35,178 -183.[ISI][Medline]
Gilbertson, T.A., Damak, S. and Margolskee, R.F. (2000) The molecular physiology of taste transduction.Curr. Opin. Neurobiol. , 10,519 -527.[ISI][Medline]
Gilmore, M.M. and Green, B.G. (1993)
Sensory irritation and taste produced by NaCl and citric acid: effects of
capsaicin desensitization. Chem. Senses,18
, 257-272.
Green, B.G. (1989) Capsaicin sensitization and desensitization on the tongue produced by brief exposures to a low concentration. Neurosci. Lett.,107 , 173-178.[ISI][Medline]
Green, B.G. (1998) Capsaicin desensitization and stimulus-induced recovery on facial compared to lingual skin. Physiol. Behav., 65,517 -523.[Medline]
Green, B.G. and Rentmeister-Bryant, H. (1998) Temporal characteristics of capsaicin desensitization and stimulus-induced recovery in the oral cavity. Physiol. Behav., 65,141 -149.[Medline]
Hamilton, R.B. and Norgren, R. (1984) Central projections of gustatory nerves in the rat. J. Comp. Neurol., 222,560 -577.[ISI][Medline]
Hayama, T., Ito, S. and Ogawa, H. (1985) Responses of solitary tract nucleus neurons to taste and mechanical stimulations of the oral cavity in decerebrate rats. Exp. Brain Res., 60,235 -242.[ISI][Medline]
Holzer, P. (1998) Neurogenic vasodilatation and plasma leakage in the skin. Gen. Pharmacol.,30 , 5-11.[ISI][Medline]
Karrer, T. and Bartoshuk, L. (1995) Effects of capsaicin desensitization on taste in humans.Physiol. Behav. , 57,421 -429.[Medline]
Kim, K.O., Ennis, D.M. and Omahony, M. (1998) A new approach to category scales of intensity II: use of d' values. J. Sensory Studies,13 , 251-267.
Kveton, J.F. and Bartoshuk, L.M. (1994) The effect of unilateral chorda tympani damage on taste.Laryngoscope , 104,25 -29.[ISI][Medline]
Lawless, H.T. (1984) Oral chemical
irritation: psychophysical properties. Chem. Senses,9
, 143-155.
Lawless, H.T. and Stevens, D.A. (1984) Effects of oral chemical irritation on taste. Physiol. Behav., 32,995 -998.[Medline]
Lawless, H.T., Rozin, P. and Shenker, J.
(1985) Effect of oral capsaicin on gustatory, olfactory and
irritant sensations and flavor identification in humans who regularly or
rarely consume chili pepper. Chem. Senses,10
, 579-589.
Lehman, C.D., Bartoshuk, L.M., Catalanotto, F.C., Kveton, J.F. and Lowlicht, R.A. (1995) Effect of anesthesia of the chorda tympani nerve on taste perception in humans.Physiol. Behav. , 57,943 -951.[Medline]
Lenz, F.A., Gracely, R.H., Zirh, T.A., Leopold, D.A., Rowland,
L.H. and Dougherty, P.M. (1997) Human thalamic
nucleus mediating taste and multiple other sensations related to ingestive
behavior. J. Neurophysiol., 77,3406
-3409.
Liu, L. and Simon, S.A. (1996)
Similarities and differences in the currents activated by capsaicin,
piperine, and zingerone in rat trigeminal ganglion cells. J.
Neurophysiol., 76,1858
-1869.
Liu, L., Welch, J.M., Erickson, R.P., Reinhart, P.H. and Simon, S.A. (2000) Different responses to repeated applications of zingerone in behavioral studies, recordings from intact and cultured TG neurons, and from VR1 receptors. Physiol. Behav., 69,177 -186.[Medline]
Liu, L., Oortgiesen, M., Li, L. and Simon, S.A.
(2001) Capsaicin inhibits activation of voltage-gated sodium
currents in capsaicin-sensitive trigeminal ganglion neurons. J.
Neurophysiol., 85,745
-758.
McMahon, D.B., Shikata, H. and Breslin, P.A.
(2001) Are human taste thresholds similar on the right and
left sides of the tongue? Chem. Senses,26
, 875-883.
McPheeters, M., Hettinger, T.P., Nuding, S.C., Savoy, L.D., Whitehead, M.C. and Frank, M.E. (1990) Taste-responsive neurons and their locations in the solitary nucleus of the hamster. Neuroscience, 34,745 -758.[ISI][Medline]
Nakamura, K. and Norgren, R. (1991)
Gustatory responses of neurons in the nucleus of the solitary tract of
behaving rats. J. Neurophysiol.,66
, 1232-1248.
Nomura, T. and Ogawa, H. (1985) The taste and mechanical response properties of neurons in the parvicellular part of the thalamic postero-medial ventral nucleus of the rat.Neurosci. Res. , 3,91 -105.[Medline]
Ogawa, H., Imoto, T. and Hayama, T. (1984) Responsiveness of solitario-parabrachial relay neurons to taste and mechanical stimulation applied to the oral cavity in rats.Exp. Brain Res. , 54,349 -358.[ISI][Medline]
Ogawa, H., Hayama, T. and Yamashita, Y. (1988) Thermal sensitivity of neurons in a rostral part of the rat solitary tract nucleus. Brain Res.,454 , 321-331.[ISI][Medline]
Osada, K., Komai, M., Bryant, B.P., Suzuki, H., Goto, A.,
Tsunoda, K., Kimura, S. and Furukawa, Y. (1997)
Capsaicin modifies responses of rat chorda tympani nerve fibers to
NaCl. Chem. Senses, 22,249
-255.
Prescott, J. and Stevenson, R.J. (1995) Effects of oral chemical irritation on tastes and flavors in frequent and infrequent users of chili. Physiol. Behav.,58 , 1117-1127.[Medline]
Prescott, J. and Swain-Campbell, N.
(2000) Responses to repeated oral irritation by capsaicin,
cinnamaldehyde and ethanol in PROP tasters and non-tasters. Chem.
Senses, 25,239
-246.
Prescott, J., Allen, S. and Stephens, L.
(1993) Interactions between oral chemical irritation, taste
and temperature. Chem. Senses, 18,389
-404.
Pritchard, T.C., Hamilton, R.B., Morse, J.R. and Norgren, R. (1986) Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis. J. Comp. Neurol., 244,213 -228.[ISI][Medline]
Pritchard, T.C., Hamilton, R.B. and Norgren, R.
(1989) Neural coding of gustatory information in the thalamus
of Macaca mulatta. J. Neurophysiol.,61
, 1-14.
Scott, T.R., Yaxley, S., Sienkiewicz, Z.J. and Rolls,
E.T. (1986) Gustatory responses in the nucleus tractus
solitarius of the alert cynomolgus monkey. J.
Neurophysiol., 55,182
-200.
Shikata, H., McMahon, D.B. and Breslin, P.A. (2000) Psychophysics of taste lateralization on anterior tongue. Percept. Psychophys., 62,684 -694.[ISI][Medline]
Simons, C.T., Dessirier, J.M., Carstens, M.I., O'Mahony, M.
and Carstens, E. (1999) Neurobiological and
psychophysical mechanisms underlying the oral sensation produced by carbonated
water. J. Neurosci., 19,8134
-8144.
Smith, D.V., John, S.J. and Boughter, J.D. (2000) Neuronal cell types and taste quality coding.Physiol. Behav. , 69,77 -85.[Medline]
Sostman, A.L. and Simon, S.A. (1991) Trigeminal nerve responses in the rat elicited by chemical stimulation of the tongue. Arch. Oral Biol., 36,95 -102.[ISI][Medline]
Stevens, D.A. and Lawless, H.T. (1987) Enhancement of responses to sequential presentation of oral chemical irritants. Physiol. Behav., 39,63 -65.[Medline]
Stevenson, R.J. and Prescott, J. (1997) Judgments of chemosensory mixtures in memory. Acta Psychol., 95,195 -214.[Medline]
Sweazey, R.D. and Bradley, R.M. (1988) Responses of lamb nucleus of the solitary tract neurons to chemical stimulation of the epiglottis. Brain Res.,439 , 195-210.[ISI][Medline]
Szolcsányi, J. (1977) A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. J. Physiol.,73 , 251-259.
Todrank, J. and Bartoshuk, L.M. (1991) A taste illusion: taste sensation localized by touch. Physiol. Behav., 50,1027 -1031.[Medline]
Tominaga, M., Caterina, M.J., Malmberg, A.B., Rosen, T.A., Gilbert, H., Skinner, K., Raumann, B.E., Basbaum, A.I. and Julius, D. (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron,21 , 531-543.[ISI][Medline]
Travers, S.P. and Norgren, R. (1995)
Organization of orosensory responses in the nucleus of the solitary tract
of rat. J. Neurophysiol., 73,2144
-2162.
Travers, S.P., Pfaffmann, C. and Norgren, R. (1986) Convergence of lingual and palatal gustatory neural activity in the nucleus of the solitary tract. Brain Res.,365 , 305-320.[ISI][Medline]
Wang, Y., Erickson, R.P. and Simon, S.A.
(1995) Modulation of rat chorda tympani nerve activity by
lingual nerve stimulation. J. Neurophysiol.,73
, 1468-1483.
Warren, R.P., Warren, R.M. and Weninger, M.G. (1969) Inhibition of the sweet taste by Gymnema sylvestre. Nature, 223,94 -95.[Medline]
Yamamoto, T. (1984) Taste responses of cortical neurons. Prog. Neurobiol.,23 , 273-315.[ISI][Medline]
Yanagisawa, K., Bartoshuk, L.M., Catalanotto, F.A., Karrer, T.A. and Kveton, J.F. (1998) Anesthesia of the chorda tympani nerve and taste phantoms. Physiol. Behav.,63 , 329-335.[Medline]
Accepted January 18, 2002
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. C. Albin, M. I. Carstens, and E. Carstens Modulation of Oral Heat and Cold Pain by Irritant Chemicals Chem Senses, January 1, 2008; 33(1): 3 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Carstens, K. C. Albin, C. T. Simons, and M. I. Carstens Time Course of Self-Desensitization of Oral Irritation by Nicotine and Capsaicin Chem Senses, November 1, 2007; 32(9): 811 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lim and B. G. Green The Psychophysical Relationship between Bitter Taste and Burning Sensation: Evidence of Qualitative Similarity Chem Senses, January 1, 2007; 32(1): 31 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Simons, Y. Boucher, M. I. Carstens, and E. Carstens Nicotine Suppression of Gustatory Responses of Neurons in the |