Selective removal of a target stimulus localized by taste in humans

Recent studies have shown that people can localize a punctate gustatory stimulus on the lingual epithelium in the absence of discriminative tactile cues. The present studies examined the human ability to localize taste sensations on the tongue and to use this information to remove selectively a target stimulus (a flavored, 1 cm(3) gelatin cube) from the mouth when presented with non-target distractors that vary in number and taste. Findings indicate that humans are capable of localizing and removing either an aversive or an appetitive gustatory target from a field of tactile distractors via taste sensations alone, although this ability diminishes as the number of distractors increases (implicating serial searches, rather than parallel). In addition, humans can localize and selectively remove a target taste in the presence of distractors of another distinct taste quality. Under these conditions performance is either unaffected or reduced, which indicates that contrast with the distinct taste of the distractors does not enhance performance. Humans also are capable of removing a nearly tasteless cube from a field of flavored distractors, but this is clearly a more difficult task, suggesting that 'tactile capture' of taste occurs for the tasteless target cube and interferes with the localization of taste. Finally, perceived suprathreshold stimulus intensity did not seem to be related to the ability to localize and remove a target stimulus via taste sensations and failed to account for variations in performance across individuals.     

Sensory interactions between capsaicin and temperature in the oral cavity

The interaction between thermal and chemical stimulation inthe oral cavity was studied in two experiments by measuringthe perceived intensity of thermal sensations in the presenceof capsaicin, and the perceived intensity of the ‘burning’sensations produced by capsaicin at several solution temperatures.It is demonstrated in the first experiment that capsaicin intensifiessensations of warmth (particularly at moderateto-high temperatures)and slightly but consistently reduces the intensity of perceivedcold. On the other hand, the burning sensation induced by capsaicinis enhanced by warming and inhibited by cooling. The secondexperiment confirmed the existence of a second inhibitory factorin addition to cooling, possibly of tactile origin. Viewed togetherthe results of both experiments indicate that complex sensoryinteractions may take place in the trigeminal system duringsimultaneous chemical, thermal and mechanical stimulation.     

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.     

Tactile interaction with taste localization: influence of gustatory quality and intensity

Taste is always accompanied by tactile stimulation, but little is known about how touch interacts with taste. One exception is evidence that taste can be "referred" to nearby tactile stimulation. It was recently found (Lim J, and Green BG. 2007. The psychophysical relationship between bitter taste and burning sensation: evidence of qualitative similarity. Chem Senses. 32:31-39) that spatial discrimination of taste was poorer for bitterness than for other tastes when the perceived intensities were matched. We hypothesized that this difference may have been caused by greater referral of bitterness by touch. The present study tested this hypothesis by comparing localization of quinine sulfate and sucrose under conditions that minimized and maximized the opportunity for referral. In both conditions, stimulation was produced by 5 cotton swabs spaced 1 cm apart and arranged in an arc to enable simultaneous contact with the front edge of the tongue. Only one swab contained the taste stimulus, whereas the rest were saturated with deionized water. In both conditions, the swabs were stroked up-and-down against the tongue 5 times. Subjects were asked to identify which swab contained the taste stimulus 1) 5 s after the fifth stroke (touch-removed condition) and 2) immediately at the end of the fifth stroke, with the swabs still in contact with the tongue (touch-maintained condition). Ratings of taste intensity were obtained to assess the possible effect of perceived intensity on spatial localization. Taste localization was surprisingly accurate, especially for sucrose, with errors of localization in the range of 1 cm or less. For both stimuli, localization tended to be poorer when the tactile stimulus was present while subjects made their judgments, but the difference between conditions was significant only for the lower concentration of quinine. The results are discussed in terms of both the surprisingly good spatial acuity of taste and the possibility of having a close perceptual relationship between touch and bitter taste.     

Attenuation of self-generated tactile sensations is predictive, not postdictive

When one finger touches the other, the resulting tactile sensation is perceived as weaker than the same stimulus externally imposed. This attenuation of sensation could result from a predictive process that subtracts the expected sensory consequences of the action, or from a postdictive process that alters the perception of sensations that are judged after the event to be self-generated. In this study we observe attenuation even when the fingers unexpectedly fail to make contact, supporting a predictive process. This predictive attenuation of self-generated sensation may have evolved to enhance the perception of sensations with an external cause.     

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.     

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.     

The effects of heat-induced pain on the detectability,discriminability, and sensation magnitude of vibrotactile stimuli

The effects of heat-induced pain on absolute thresholds, sensation magnitudes and amplitude-difference thresholds were measured at 10 and 100 Hz. Consistent with previous results, heat-induced pain elevated the absolute thresholds by approximately 8.0 dB and lessened the magnitudes of tactile sensations during pain as compared to the non-painful condition. In contrast to these effects, the discriminability of change in the intensity of the vibrotactile stimuli was unaffected by the presence of pain indicating that the effect of pain on tactile sensations is more likely due to sensory rather than cognitive processes (i.e., attention) and that the mechanisms underlying tactile sensitivity as compared to discriminability are different.     

The effects of heat-induced pain on the detectability, discriminability, and sensation magnitude of vibrotactile stimuli

The effects of heat-induced pain on absolute thresholds, sensation magnitudes and amplitude-difference thresholds were measured at 10 and 100 Hz. Consistent with previous results, heat-induced pain elevated the absolute thresholds by approximately 8.0 dB and lessened the magnitudes of tactile sensations during pain as compared to the non-painful condition. In contrast to these effects, the discriminability of change in the intensity of the vibrotactile stimuli was unaffected by the presence of pain indicating that the effect of pain on tactile sensations is more likely due to sensory rather than cognitive processes (i.e., attention) and that the mechanisms underlying tactile sensitivity as compared to discriminability are different.     

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.     

Capsaicin as a cutaneous stimulus: sensitivity and sensory qualities on hairy skin

An experiment was conducted to investigate the sensitivity ofthe skin to capsaicin. Whereas most previous work on capsaicin'scutaneous (extra-oral) effects have focused on its ability tosensitize or desensitize the skin to subsequent stimulation,the present study measured the absolute sensitivity to, andthe sensations produced by, transient exposures to capsaicin.A wide range of concentrations of capsaicin was presented tothe volar forearm under conditions that prevented significantevaporation for the first 10 min of exposure, and subjects reportedthe sensations they experienced over a 20-min period. The resultsshowed that capsaicin produced a variety of sensations (includingitch, stinging/pricking and burning) that varied in time andfrequency of appearance. Missing from the subjective reportswas a significant thermal component to the sensation; capsaicinapparently failed to stimulate warm fibers either strongly orreliably. Overall, however, the variety of sensations inducedby capsaicin reflects the multi-modal nature of the chemicalsensitivity of the skin.     

The Influence of Rate of Skin Indentation on Threshold and Suprathreshold Tactile Sensations

The effects of skin indentation depth and rate on threshold and suprathreshold tactile sensations were investigated. Indentation rates between 0.3 and 10 mm/sec had little effect on the absolute tactile thresholds measured in terms of indentation depth. Slower rates resulted in increased absolute thresholds.

Estimates of the growth in intensity of tactile sensations were made as functions of indentation depth and rate. The fastest rate used (10 mm/sec), for a given depth of indentation, produced the most intense sensation; the slowest (0.1 mm/sec), the least intense sensation. The tactile sensation magnitude estimates, with rate as the parameter, could be described by power functions. At the slowest indentation rate the exponent of the function was 1.36. At faster indentation rates (0.4, 1.0, and 10 mm/sec), two functions of markedly different slopes were required to describe the estimates. The exponents of the power functions were between 0.38 and 0.49 for indentation depths up to about 0.9 mm, and between 1.07 and 1.43 for deeper indentation depths.     

The influence of topical capsaicin on the local thermal control of skin blood flow in humans

To test whether heat-sensitive receptors participate in the cutaneous vascular responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler flowmetry) where the sensation of heat was induced either by local warming (T(Loc); Peltier cooling/heating unit) or by both direct warming and chemical stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical capsaicin (0.075 or 0.025%) was applied to 12 cm(2) of skin 1 h before stepwise local warming of untreated and capsaicin-treated forearm skin. Pretreatment with 0.075% capsaicin cream shifted the SkBF/T(Loc) relationship to lower temperatures by an average of 6 +/- 0.8 degrees C (P < 0.05). In part II, we used a combination of topical capsaicin (0.025%) and local warming to evoke thermal sensation at one site and only local warming to evoke thermal sensation at a separate site. Cutaneous vasomotor responses were compared when the temperatures at these two sites were perceived to be the same. SkBF differed significantly between capsaicin and control sites when compared on the basis of actual temperatures, but that difference became insignificant when compared on the basis of the perceived temperatures. These data suggest heat-sensitive nociceptors are important in the cutaneous vasodilator response to local skin warming.     

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.     

Topically applied capsaicin inhibits sensitivity to touch but not to warmth or heat-pain in the region of secondary mechanical hyperalgesia

The aim of this study was to investigate tactile sensitivity near the site of primary hyperalgesia evoked by capsaicin applied topically to the dorsolateral aspect of the hand. In the first experiment (N = 15), touch thresholds increased in the fifth finger ipsilateral to the topically applied capsaicin, but remained unchanged at greater distances from the site of capsaicin treatment. In a second experiment (N = 12), the effect of the capsaicin treatment on sensations evoked not only by light touch but also by warmth, heat-pain, and pressure-pain to a 2-mm diameter steel probe was investigated in the fifth finger. Again, tactile sensitivity was inhibited at the fifth finger, even though stimulation with a cotton bud evoked no discomfort; moreover, sensitivity to warmth and heat-pain were unimpaired. However, sensitivity to pressure-pain increased in the fifth finger after the capsaicin treatment, possibly due to activation of nociceptors sandwiched between the probe tip and bone that normally responded to sharp stimuli. These findings suggest that the central mechanisms that mediate secondary mechanical hyperalgesia suppress sensitivity to innocuous tactile sensations. This effect may contribute to tactile hypoesthesia in chronic pain conditions.     

Interactions between Chemical and Thermal Cutaneous Stimuli: Inhibition (Counterirritation) and Integration

Methyl salicylate, a commonly used chemical counterirritant, was applied topically to the forearm to determine whether a nonpainful chemical irritation could inhibit the perception of another (weaker) chemical irritation. In the first experiment, sensations of irritation (burning and stinging) produced by a 10% solution of methyl salicylate were significantly attenuated when a 15% solution of the same chemical was applied to the opposite forearm. In the second experiment, neither the perception of warmth nor the heat pain threshold was affected by application of 10% or 15% methyl salicylate to a site 10 cm from the thermal stimulus. Inhibition did, however, occur in the opposite direction: Chemical irritation was reduced after the thermal stimulus reached a painful level. In the third experiment, a 15% solution of methyl salicylate was applied immediately adjacent to the thermal stimulus, with the result that ratings of warmth intensity increased rather than decreased, and perceived irritation was again attenuated following a painful heat stimulus. Overall, the results indicate that (1) chemical counterirritation can occur at nonpainful levels; (2) the resulting inhibition is confined to the nociceptive system; and (3) when the nociceptive and warmth systems are activated together, the tendency is toward integration rather than inhibition.     

Interactions between chemical and thermal cutaneous stimuli: inhibition (counterirritation) and integration.

Methyl salicylate, a commonly used chemical counterirritant, was applied topically to the forearm to determine whether a nonpainful chemical irritation could inhibit the perception of another (weaker) chemical irritation. In the first experiment, sensations of irritation (burning and stinging) produced by a 10% solution of methyl salicylate were significantly attenuated when a 15% solution of the same chemical was applied to the opposite forearm. In the second experiment, neither the perception of warmth nor the heat pain threshold was affected by application of 10% or 15% methyl salicylate to a site 10 cm from the thermal stimulus. Inhibition did, however, occur in the opposite direction: Chemical irritation was reduced after the thermal stimulus reached a painful level. In the third experiment, a 15% solution of methyl salicylate was applied immediately adjacent to the thermal stimulus, with the result that ratings of warmth intensity increased rather than decreased, and perceived irritation was again attenuated following a painful heat stimulus. Overall, the results indicate that (1) chemical counterirritation can occur at nonpainful levels; (2) the resulting inhibition is confined to the nociceptive system; and (3) when the nociceptive and warmth system are activated together, the tendency is toward integration rather than inhibition.     

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.     

Olfaction and the common chemical sense: some psychophysical contrasts.

Three experiments explored the olfactory and the common chemical attributes of sensations produced by various concentrations of n-butyl alcohol. These two attributes combine in an almost-linear fashion to produce the overall perceived intensity of the stimulus. Common chemical intensity makes only a small contribution to overall magnitude at low concentrations, but its proportional contribution increases with concentration. In like manner, speed of response (i.e., reciprocal of reaction time) to the common chemical attribute increases more rapidly than that to odor. Nevertheless, odor always makes its appearance sooner than the common chemical attribute, even when the two attributes are matched in perceived magnitude. Repeated inhalations cause odor intensity to decrease slightly but cause common chemical intensity to increase dramatically. The results obtained from the normal subjects studied here agree with those obtained from subjects with unilateral destruction of the trigeminal nerve.     

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.