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Biomedical subjects

Barry G Green

Publications and source records attributed to Barry G Green.

14 recordsLinked to original sources

Thermal and nociceptive sensations from menthol and their suppression by dynamic contact.

It was recently found that cooling the skin to temperatures as mild as 25-30 degrees C can induce nociceptive sensations (burning, stinging or pricking) that are strongly suppressed by dynamic contact between the thermode and skin (contact suppression). Here we investigated whether nociceptive sensations produced by menthol can be similarly suppressed. In the first experiment subjects rated the intensity of cold and burning/stinging/pricking sensations before and after application of 10% l-menthol to the forearm. Ratings were compared at resting skin temperature ( approximately 33 degrees C) and at 28, 24, or 20 degrees C during static or dynamic contact cooling via a Peltier thermode. At resting skin temperature, menthol produced cold and nociceptive sensations, both of which were suppressed by dynamic contact. When the skin was cooled during static contact, menthol increased nociceptive sensations but not cold sensations; when the skin was cooled during dynamic contact, cold sensations were again unchanged while nociceptive sensations were suppressed. A second experiment tested whether contact suppression of menthol's cold and nociceptive sensations at resting skin temperature was caused by slight deviations of thermode temperature above skin temperature. The results showed that suppression occurred even when the thermode was slightly cooler (-0.5 degrees C) than the skin. These findings support other evidence that the menthol-sensitive channel, TRPM8, plays a role in cold nociception, and raise new questions about how dynamic tactile stimulation may modify perception of nonpainful cold stimulation.

Adolescent↗

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.

Adolescent↗

Chemesthesis and taste: evidence of independent processing of sensation intensity.

The ability to perceive taste from temperature alone ("thermal taste") was recently shown to predict higher perceptual responsiveness to gustatory and olfactory stimuli. This relationship was hypothesized to be due in part to individual differences in CNS processes involved in flavor perception. Here we report three experiments that tested whether subjects who differ in responsiveness to thermal taste and/or chemical taste also differ in responsiveness to oral chemesthesis. In experiment 1, subjects identified as 'thermal tasters' (TTs) or 'thermal non-tasters' (TnTs) used the general Labeled Magnitude Scale to rate the intensity of sensations produced on the tongue tip by capsaicin, menthol, sucrose, NaCl, citric acid, and QSO4. TTs rated all four taste stimuli higher than did TnTs, whereas sensations of burning/stinging/pricking and temperature from capsaicin and menthol did not differ significantly between groups. In experiment 2, testing with capsaicin on both the front and back of the tongue confirmed there was no difference in ratings of burning/stinging/pricking when subjects were grouped according to the ability to perceive thermal taste. In experiment 3, subjects were classified as high- or low-tasters according to their ratings of sucrose sweetness rather than thermal taste. No group difference was found for perception of capsaicin even when presented in mixture with sucrose or NaCl. The results are discussed in the context of previous evidence of an association between chemesthesis and sensitivity to the bitter tastant PROP, and in terms of the various peripheral and central neural processes that may underlie intensity perception in taste and chemesthesis.

Adolescent↗

Evidence that tactile stimulation inhibits nociceptive sensations produced by innocuous contact cooling.

It was recently shown that stinging, pricking or burning is reliably perceived by some individuals when the skin is cooled to temperatures as mild as 25-30 degrees C. These seemingly paradoxical sensations, which have been termed innocuous-cold nociception (ICN), were significant only when cooling was produced by a thermode resting statically on the skin (static contact); touching an already cooled thermode to the skin (dynamic contact) produced reports of only coolness and cold. The present study investigated the hypothesis that ICN is inhibited by tactile stimulation produced when a thermode contacts the skin. Experiment 1 pitted the tactile hypothesis against an alternative explanation that inhibition results from higher rates of skin cooling during dynamic contact. ICN was measured at three different cooling rates (-1.0, -2.5, -5.0 degrees C/s) when the thermode was resting on the skin or was touched to the skin at the moment cooling began. The results supported the tactile hypothesis: faster cooling rates during static contact led to stronger rather than weaker nociceptive sensations, and ICN was suppressed even when dynamic contact was coincident with the onset of cooling, and thus could not affect cooling rate. Experiment 2 confirmed the latter result and showed that suppression was greatest at 28 degrees C, less at 24 degrees C, and not significant at 18 degrees C. We conclude that dynamic tactile stimulation produced by contact with a surface inhibits the nociceptive component of innocuous but not noxious cooling. The implications of this conclusion for the role of cold perception in behavioral thermoregulation versus haptic perception, and for theories of cold perception in general, are discussed.

Adult↗

Temperature perception and nociception.

The specificity theory of somesthesis holds that perceptions of warmth, cold, and pain are served by separate senses. Although no longer accepted in all its details, the theory's basic assumptions of anatomical and functional specificity have remained guiding principles in research on temperature perception and its relationship to pain. This article reviews the response characteristics of thermoreceptors, temperature-sensitive nociceptors, and their associated pathways in the context of old and new perceptual phenomena, most of which cannot be satisfactorily explained by the specificity theory. The evidence indicates that throughout most of the perceptual range, temperature sensitivity depends upon coactivation of, and interactions among, thermal and nociceptive pathways that are composed of both specific "labeled lines" and nonspecific, multimodal fibers. Adding to this complexity is evidence that tactile stimulation can influence the way in which thermal stimulation is perceived. It is argued that thermoreception is best defined as a functional subsystem of somesthesis that serves the very different and sometimes conflicting demands of thermoregulation, protection from thermal injury, and haptic perception.

Animals↗

Individual differences in perception of bitterness from capsaicin, piperine and zingerone.

It was recently shown that in some subjects capsaicin can evoke bitterness as well as burning and stinging, particularly in the circumvallate (CV) region of the tongue. Because perception of bitterness from capsaicin is characterized by large individual differences, the main goal of the present study was to learn whether people who taste capsaicin as bitter also report bitterness from structurally similar sensory irritants that are known to stimulate capsaicin-sensitive neurons. The irritancy and taste of capsaicin and two of its most commonly studied congeners, piperine and zingerone, were measured in individuals who had been screened for visibility of, and reliable access to, the CV papillae. Approximately half of these individuals reported tasting bitterness from all three irritants when the stimuli were swabbed directly onto the CV papillae. Concentrations that produced similar levels of burning sensation across subjects also produced similar (though lower) levels of bitter taste. These results are consistent with the hypothesis that capsaicin and its congeners stimulate bitterness via a common sensory receptor that is distributed differentially among individuals. Additionally, bitter tasters rated gustatory qualities (but not burning and stinging) slightly but significantly higher than did bitter non-tasters, which suggests that perception of capsaicin bitterness is associated with a higher overall taste responsiveness (but not chemesthetic responsiveness) in the CV region.

Adolescent↗

'Thermal taste' predicts higher responsiveness to chemical taste and flavor.

Individual differences in taste perception have been explained in part by variations in peripheral innervation associated with the genetic ability to taste the bitter substances PTC and PROP. In the present study we report evidence of another source of individual differences that is independent of taste stimulus, taste quality, or gustatory nerve. Individuals who perceived taste from thermal stimulation alone (thermal taste) gave significantly higher taste ratings to chemical stimuli--often by a factor of >2:1--than did individuals who perceived no taste from thermal stimulation. This was true for all taste stimuli tested (sucrose, saccharin, sodium chloride, citric acid, quinine sulfate, MSG and PROP), for all three gustatory areas of the mouth (anterior tongue, posterior tongue and soft palate) and for whole-mouth stimulation. Moreover, the same individuals reported stronger sensations from the olfactory stimulus vanillin, particularly when it was sensed retronasally. The generality of the thermal-taster advantage and its extension to an olfactory stimulus suggests that it arises from individual differences in CNS processes that are involved in perception of both taste and flavor.

Adolescent↗

Capsaicin as a probe of the relationship between bitter taste and chemesthesis.

Previous studies have indicated that capsaicin, traditionally considered to be a pure chemesthetic stimulus, can evoke a bitter taste and might also cross-desensitize the tastes of some bitter and sour tastants. The purpose of the present study was to investigate further the scope and nature of capsaicin's effects on bitter taste. In Experiment 1, subjects rated the taste and burning/stinging of QSO4 (0.32 and 1.0 mM), saccharin (1.0 and 3.2 mM), urea (3.2 and 10 M), MgCl2, (0.18 and 0.56 M), PROP (0.32 mM), and sucrose (0.32 and 1.0 M) applied to the tongue tip with cotton swabs before and after 10 applications of 300 microM capsaicin. Capsaicin initially evoked a weak bitterness in some subjects that quickly diminished over repeated exposures. Following capsaicin treatment, the bitterness of QSO4, urea, MgCl2, and PROP was reduced, as was the burning sensation produced by MgCl2 and urea. In Experiment 2, we tested 29 subjects in the circumvallate (CV) region of the tongue using the same general procedure. Capsaicin induced a weak but persistent bitterness in a subset of subjects but failed to desensitize its own bitterness or that of any other tastant. Overall, the results confirm that capsaicin can both stimulate and desensitize bitter taste, but in amounts that vary for different bitter stimuli and between the front and back of the tongue. Possible reasons for these regional and stimulus-dependent differences are discussed.

Adolescent↗

Decline of tactile acuity in aging: a study of body site, blood flow, and lifetime habits of smoking and physical activity.

Tactile acuity of 60 older subjects (> or = 65 years) and 19 younger subjects (18-28 years) was assessed by two-point gap thresholds at the upper and lower surfaces of the forefinger, at the upper and lower surfaces of the feet, and at the volar surface of the forearm. The older subjects were assigned to one of four groups of 15 subjects each, depending on reported lifetime habits of physical activity and smoking: (1) active smokers, (2) active nonsmokers, (3) inactive smokers, and (4) inactive nonsmokers. Peripheral blood flow was assessed at the forefinger, foot, and forearm by means of laser-Doppler imaging and skin temperature recordings, under resting conditions and during and after a 5-min exposure to mild cooling (28 degrees C). Consistent with previous studies, tactile acuity thresholds in the foot and finger averaged about 80% higher in the older subjects than in the younger subjects, but only about 22% higher in the forearm. Although the upper surface of the fingertip was more sensitive than the lower surface in both younger and older subjects, the age-related decline in tactile acuity was nearly identical on both sides of the finger and foot. The latter finding refutes the hypothesis that the larger effect of aging in the extremities results from greater physical wear and tear on the contact surfaces of the hands and feet. Self-reported lifetime histories of physical activity and smoking were not significantly associated with measures of cutaneous blood flow or tactile thresholds. Possible reasons for this lack of association are discussed, including the inherent limitations of testing only healthy older subjects, and the concept of "successful aging".

Adolescent↗

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.

Adolescent↗

Innocuous cooling can produce nociceptive sensations that are inhibited during dynamic mechanical contact.

In a previous study of the heat grill illusion, sensations of burning and stinging were sometimes reported when the skin was cooled by as little as 2 degrees C. Informal tests subsequently indicated that these nociceptive sensations were experienced if cooling occurred when the stimulating thermode rested on the skin, but not when the thermode was cooled and then touched to the skin. In experiment 1 subjects judged the intensity of thermal (cold/warm) and nociceptive (burning/stinging) sensations when the volar surface of the forearm was cooled to 25 degrees C (1) via a static thermode (Static condition), or (2) via a cold thermode touched to the skin (Dynamic condition). The total area of stimulation was varied from 2.6 to 10.4 cm(2) to determine if the occurrence of nociceptive sensations depended upon stimulus size. Burning/stinging was rated 10.3 times stronger in the Static condition than in the Dynamic condition, and this difference did not vary significantly with stimulus size. In experiment 2, thermal and nociceptive sensations were measured during cooling to just 31 degrees, 29 degrees or 27 degrees C, and data were obtained on the frequency at which different sensation qualities were experienced. Stinging was the most frequently reported nociceptive quality in the Static condition, and stinging and burning were both markedly reduced in the Dynamic condition. In experiment 3 we tested the possibility that dynamic contact might have inhibited burning and stinging not because of mechanical contact per se, but rather because dynamic contact caused higher rates of cooling. However, varying cooling rate over a tenfold range (-0.5 degrees to -5.0 degrees /s) had no appreciable effect on the frequency of stinging and burning. Overall, the data show that mild cooling can produce nociceptive sensations that are suppressed under conditions of dynamic mechanical contact. The latter observation suggests that cold is perceived differently during active contact with objects than during passive heat loss to the environment. Hypotheses about the physiological basis of the nociceptive sensations at mild temperatures and their possible role in the phenomena of paradoxical heat and synthetic heat are discussed.

Adult↗

Synthetic heat at mild temperatures.

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40 degrees C) and cool (> or = 27 degrees C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3 degrees C. Cooling by just 1 degrees C from a base temperature of 33 degrees C led to reports of heat on more than 1/3 of trials, and cooling by just 3 degrees C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29 degrees C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.

Adult↗

The sensory response to capsaicin during repeated topical exposures: differential effects on sensations of itching and pungency.

Changes in sensory irritation were measured during repeated topical exposures to capsaicin over 2 days. The perceived intensities of itching and pungent sensations, predominantly burning and stinging/pricking, were assessed every 60 sec during 5 applications of capsaicin at inter-stimulus intervals (ISI) of 90 min (Exp. 1) or 15 min (Exp. 2) and in follow-up tests 24 h later. Psychophysical measurements were obtained with a hand-held dynamometer in conjunction with the method of magnitude production. When the ISI was 90 min, itching and pungency were both significantly reduced (i.e., desensitization occurred) by the fifth exposure; however, the reduction occurred more rapidly and dramatically for itching. After 24 h, desensitization remained significant only for itching. When the ISI was 15 min, the sensations on day 1 first intensified in a manner consistent with sensitization, then declined in a manner consistent with desensitization; compared to pungency, itch exhibited less sensitization and more desensitization. On day 2, overall intensity was less for both categories of sensation, primarily because of a reduction in sensitization. Marked individual differences were observed in the overall sensitivity to capsaicin, the time course of sensation, the susceptibility to capsaicin-induced itch, and the rate and duration of sensitization and desensitization. The results are discussed in terms of current hypotheses about the sensory mechanisms that underlie chemically induced itch and the use of capsaicin as a topical analgesic and antipruritic.

Administration, Topical↗