Site-dependent and subject-related variations in perioral thermal sensitivity

The Marstock method of limits was used to obtain thresholds for detection of cooling, warming, cold pain and heat pain for 34 young adults, upon eight spatially matched sites on the left and right sides of the face, the right ventral forearm and the scalp. Male and female subjects were tested by both a male and a female experimenter. Neither the experimenter nor the gender of the subject individually influenced the thresholds. The thermal thresholds varied greatly across facial sites: sixfold and tenfold for cool and warmth, respectively, from the most sensitive sites on the vermilion to the least sensitive facial site, the preauricular skin. Warm thresholds were 68% higher than cool thresholds, on average, and 12% higher on the left compared to the right side of the face. The mean cold pain threshold increased from 21.0°C on the hairy upper lip to 17.8°C on the preauricular skin. Sites on the upper lip were also most sensitive to noxious heat with pain thresholds of 42–43°C. The scalp was notably insensitive to innocuous and noxious changes in temperature. For the sensations of nonpainful cool and warmth, the more sensitive a site, the less the estimates of the thresholds differed between subjects. In contrast, for heat pain, the more sensitive a site, the more the estimates differed between subjects. Subjects who were relatively more sensitive to cool tended to be relatively more sensitive to warmth. Subjects’ sensitivities to nonpainful cool and warmth were less predictive of their sensitivities to painful cold and heat, respectively. Short-term within-subject variability increased with the magnitude of the thresholds. The lower the threshold, the more similar were repeated measurements of it, within a 5–25?s period.     

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.     

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°C) and cool ( &#83 27°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°C. Cooling by just 1°C from a base temperature of 33°C led to reports of heat on more than 1/3 of trials, and cooling by just 3°C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29°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.     

Body Site Variation of Cool Perception Thresholds,with Observations on Paradoxical Heat

Thresholds for the perception of coolness and heat pain were determined in sessions that randomly intermixed temperature increases and decreases. Four body sites were tested bilaterally: thenar eminence of the hand, plantar surface of the foot, dorsolateral forearm, and lateral calf. Coolness thresholds were lowest for the hand, intermediate for the forearm, and highest for the leg and foot. Laterality differences were not statistically significant.

In 34% of the sessions, subjects did not consistently report cool or cold sensations with detectable temperatue decreases. When they did not report cool or cold, they most often reported heat or pain, thus exhibiting the phenomenon of “paradoxical heat”. There were significantly more paradoxical heat responses when cooling stimuli were intermixed with painfully hot stimuli than when they were intermixed with only warm stimuli.

There was no significant correlation observed between thresholds for coolness and heat pain, either across body sites or across subjects at any single body site. This result implies that the various factors relevant to thermal sensitivity (i.e., thermal properties of the epidermis, innervation density) are differentially important for cool versus heat pain perception.     

Afferent Modulation of Warmth Sensation and Heat Pain in the Human Hand

The hands of 14 normal humans were used to determine the somatotopic organization of the modulation of warmth sensation and heat pain by different forms of cutaneous stimuli. Test stimuli were 5-sec heat pulses ranging from 36° to 51°C, delivered to the fingerpads of digits 1, 2, 4, and 5 with a contact thermode. Conditioning stimuli (15 sec) bracketed the test stimuli and included vibration, noxious and innocuous heat, cold, and electrical pulses delivered to the fingerpads of digits that were adjacent or nonadjacent to the tested digits. Noxious (48° ± 1.3°C), but not innocuous (43°C), heat stimuli increased the perceived magnitude estimation of innocuous test stimuli (36–43°C) by 20–37% when delivered to adjacent, but not to nonadjacent, digits. No other conditioning stimuli had any effect on the intensity of warmth perception. In contrast, both noxious and innocuous heat or electrical conditioning reduced the magnitude estimation of noxious (50–5°C), but not innocuous, test pulses by 12–22% when delivered to adjacent digits. Conditioning of nonadjacent digits was significantly less effective. The analgesic effects of noxious and innocuous conditioning were approximately equal. Vibratory (120 Hz, 3.5 μm) and cold (15°C) conditioning stimuli were ineffective. The results are consistent with a dermatomal somatotopic organization of tactile and heat modulatory influences on warmth sensation and heat pain. The results further suggest that the neural mechanisms subserving warmth mediate a negative feedback influence on heat pain intensity.     

Individual differences in temperature perception: evidence of common processing of sensation intensity of warmth and cold

The longstanding question of whether temperature is sensed via separate sensory systems for warmth and cold was investigated by measuring individual differences in perception of nonpainful heating and cooling. Sixty-two subjects gave separate ratings of the intensity of thermal sensations (warmth, cold) and nociceptive sensations (burning/stinging/pricking) produced by cooling (29 degrees C) or heating (37 degrees C) local regions of the forearm. Stimuli were delivered via a 4 x 4 array of 8 mm x 8 mm Peltier thermoelectric modules that enabled test temperatures to be presented sequentially to individual modules or simultaneously to the full array. Stimulation of the full array showed that perception of warmth and cold were highly correlated (Pearson r = 0.83, p < 0.05). Ratings of nonpainful nociceptive sensations produced by the two temperatures were also correlated, but to a lesser degree (r = 0.44), and the associations between nociceptive and thermal sensations (r = 0.35 and 0.22 for 37 and 29 degrees C, respectively) were not significant after correction for multiple statistical tests. Intensity ratings for individual modules indicated that the number of responsive sites out of 16 was a poor predictor of temperature sensations but a significant predictor of nociceptive sensations. The very high correlation between ratings of thermal sensations conflicts with the classical view that warmth and cold are mediated by separate thermal modalities and implies that warm-sensitive and cold-sensitive spinothalamic pathways converge and undergo joint modulation in the central nervous system. Integration of thermal stimulation from the skin and body core within the thermoregulatory system is suggested as the possible source of this convergence.     

The perception of painful and nonpainful stimuli during voluntary motor activity in man

Previous studies have shown that voluntary movement diminishes the transmission of cutaneous afferent input through the dorsal column-medial lemniscal system, and also raises the threshold for detecting nonpainful, cutaneous stimuli (electrical shocks). Although there is some evidence that pain elicited by electrical stimulation is diminished during movement, no studies have tested the effect of movement on the perception of pain produced by natural stimulation. For this reason, we tested the effects of voluntary motor activity on the perception of noxious thermal stimuli in human volunteers. We first developed a motor paradigm in which the thermal stimulation could be applied to the immobile limb (isometric elbow flexion-extension). Both isometric and isotonic muscle contractions about the elbow increased the threshold for detecting weak cutaneous stimuli (electrical shocks) applied to the forearm, and to a lesser extent the detection of stimuli applied to the dorsum of the hand. Afterwards, noxious and innocuous heat stimuli were applied to the forearm during isometric contractions and at rest. Magnitude estimates for the intensity of the pain, as well as latency measures of the onset of pain, were recorded. We found no evidence that isometric motor activity diminished either the threshold for pain or the subjective intensity of the noxious and innocuous thermal stimuli. Thus, motor activity decreases the ability to detect weak low-threshold cutaneous inputs, but has no effect on the perception of warmth and heat pain.     

Frequency and site-dependent variations in vibration detection thresholds on the face

An adaptive psychophysical procedure was used to estimate the vibration detection threshold at seven spatially matched sites on the two sides of the face and at one scalp site. Repeated measurements over six testing sessions were made for stimuli vibrating at 1, 10 and 100 Hz for each of 21 neurologically healthy, young adult females. Approximately 14 stimulus trials were required to obtain each estimate of the threshold amplitude. Thresholds varied as a function of frequency (p < 0.0001), side (p < 0.001) and site (p < 0.0001). Compared to stimulation at 100 Hz at which the estimates were lowest, thresholds were 3.1 times greater at 10 Hz and 5.4 times greater at 1 Hz. Thresholds were lowest on the vermilion and highest on the cheek and chin. The preauricular skin and scalp exhibited an intermediate level of sensitivity. Whereas thresholds were comparable on the two sides of the face for stimulation at 1 Hz, they averaged 1.33 times greater on the right side for stimulation at 10 and 100Hz. Moreover, thresholds obtained during the last two sessions were 16% higher than those obtained during the first two sessions (p < 0.02), suggesting that subjects on average became more conservative in reporting the presence of the stimulus. The sensitivity in discriminating differences in tactile function favors use of the rapidly administered testing procedure in a clinical setting.     

Comparison of unpleasant and pain thresholds of thermal stimuli in the orofacial regions: a psychophysical study using quantitative sensory testing in healthy young men

Abstract

Purpose/Aim: To gain a better understanding of the psychophysics of thermal pain perception in a clinical setting, this study investigated whether thermal thresholds of unpleasantness are different from pain thresholds of cold and heat stimuli. Of particular interest was the relationship between unpleasantness and pain thresholds for cold vs heat stimuli.

Material and methods: Thirty healthy male volunteers (mean age 26.1?years, range 23 to 32?years) participated. Thermal detection, cold pain (CPT) and heat pain (HPT) thresholds were measured at 5 trigeminal sites by the method of limits using quantitative sensory testing (QST), followed by cold unpleasant (CUT) and heat unpleasant (HUT) thresholds.

Results: The temperatures at which individuals first reported thermal sensations as unpleasant or painful substantially differed among subjects. CUT exhibited a higher mean value with less variability than CPT, and HUT presented a lower mean than HPT (p?<?.001). As with CPT, CUT did not show any significant difference between the test sites. On the other hand, HUT, like HPT, exhibited site differences (p?<?.001). There was moderate correlation between CUT and CPT, whereas HUT and HPT were strongly correlated. The relationship between unpleasant and pain thresholds of cold vs heat stimuli was significantly different even when controlling for test site variability (p?<?.001).

Conclusion: These findings indicate that unpleasant and pain thresholds to thermal stimuli differ in healthy young men. Of particular note is the distinct relationship of unpleasant and pain thresholds of cold vs heat stimuli, revealing the thermal difference in temperature transition from unpleasantness to pain.     

Stimulus features relevant to the perception of sharpness and mechanically evoked cutaneous pain

Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception.     

Frequency and site-dependent variations in vibration detection thresholds on the face

An adaptive psychophysical procedure was used to estimate the vibration detection threshold at seven spatially matched sites on the two sides of the face and at one scalp site. Repeated measurements over six testing sessions were made for stimuli vibrating at 1, 10 and 100 Hz for each of 21 neurologically healthy, young adult females. Approximately 14 stimulus trials were required to obtain each estimate of the threshold amplitude. Thresholds varied as a function of frequency ( p < 0.0001), side ( p < 0.001) and site ( p < 0.0001). Compared to stimulation at 100 Hz at which the estimates were lowest, thresholds were 3.1 times greater at 10 Hz and 5.4 times greater at 1 Hz. Thresholds were lowest on the vermilion and highest on the cheek and chin. The preauricular skin and scalp exhibited an intermediate level of sensitivity. Whereas thresholds were comparable on the two sides of the face for stimulation at 1 Hz, they averaged 1.33 times greater on the right side for stimulation at 10 and 100 Hz. Moreover, thresholds obtained during the last two sessions were 16% higher than those obtained during the first two sessions ( p < 0.02), suggesting that subjects on average became more conservative in reporting the presence of the stimulus. The sensitivity in discriminating differences in tactile function favors use of the rapidly administered testing procedure in a clinical setting.     

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.     

Cutaneous thermal thresholds of tropical indigenes residing in Japan

The purpose of this study was to examine the deacclimatization of the cutaneous thermal sensations of tropical indigenes residing in temperate climates. Tropical indigenes (n=13) who were born and raised in tropics but had resided in Japan for 5–61 months participated in this study, along with temperate indigenes (n=11). Their cutaneous thermal thresholds for warm, cool, hot, and cold sensations were measured in 12 body regions using a thermal stimulator controlled by a Peltier element and a push button switch. Subjects pressed the button-switch as soon as they perceived a feeling of being ‘slightly warm’, ‘slightly cool’, ‘hot’, or ‘cold’ from a neutral thermal state. Our results showed that: (1) among the tropical indigenes, no significant relationship was found between the duration of their stay in Japan and their cutaneous thermal thresholds; (2) the tropical indigenes were, on average, 3.3, 3.5, 4.2, and 7.3 °C less sensitive to warm, hot, cool, and cold sensations, respectively, than the temperate indigenes (P<0.05); and (3) the inter-threshold sensory zones between cutaneous warmth and coolness, and hot and cold sensations were wider among the tropical indigenes than among the temperate indigenes. It was concluded that the nature of the heat acclimatization of the cutaneous thermal thresholds for the tropical indigenes was retained despite their residence in a temperate climate for up to 61 months, indicating that they had more blunted perceptions of both warming and cooling than the temperate indigenes.     

Thermosensory intensity and affect throughout the perceptible range

The thermosensory system was evaluated psychophysically in 12 healthy volunteers, spanning the full range of tolerable temperatures. Subjects provided ratings of (1) perceived thermal intensity, (2) perceived pleasantness or unpleasantness, and (3) perceived pain intensity after placing either one hand or foot in a temperature controlled water bath. Of particular interest were the interrelationships among the three perceptual measures, and differences between heat and cold. The relationship between perceived intensity and (un)pleasantness was different for hot vs cold stimuli. Specifically, for a given perceived thermal intensity, cold stimuli were rated as less pleasant or more unpleasant than hot stimuli. Similarly, for a given pain intensity, cold stimuli were rated as more unpleasant than hot stimuli. As warm temperatures increased and as cold temperatures decreased, stimuli were perceived as being unpleasant before they were perceived as being painful. The difference in transition temperatures for unpleasantness vs pain for heat averaged 1.4 degrees C, while the same difference for cold averaged 5.6 degrees C. Thus, there was a fourfold difference in the range of unpleasant but non-painful cold vs hot temperatures. Pain intensity and unpleasantness ratings were significantly higher for heat stimuli applied to the foot vs hand. In contrast, there was no significant body site difference for pain intensity or unpleasantness ratings of cold stimuli. All of these results reveal important differences in the processing of cold vs hot stimuli. These differences could be exploited to differentiate processing relevant to discriminative vs affective components of somesthetic perception, in both the innocuous and noxious ranges.     

How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation

Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful) temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP) family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermosensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious cold sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in cold sensation needs to be confirmed. Thus, the molecular logic for the perception of cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these cold thermoreceptors, as well as address the current controversy regarding TRPA1 and cold signaling.     

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.     

Significant Determinants of Mouse Pain Behaviour

Transgenic mouse behavioural analysis has furthered our understanding of the molecular and cellular mechanisms underlying damage sensing and pain. However, it is not unusual for conflicting data on the pain phenotypes of knockout mice to be generated by reputable groups. Here we focus on some technical aspects of measuring mouse pain behaviour that are often overlooked, which may help explain discrepancies in the pain literature. We examined touch perception using von Frey hairs and mechanical pain thresholds using the Randall-Selitto test. Thermal pain thresholds were measured using the Hargreaves apparatus and a thermal place preference test. Sodium channel Nav1.7 knockout mice show a mechanical deficit in the hairy skin, but not the paw, whilst shaving the abdominal hair abolished this phenotype. Nav1.7, Nav1.8 and Nav1.9 knockout mice show deficits in noxious mechanosensation in the tail, but not the paw. TRPA1 knockout mice, however, have a loss of noxious mechanosensation in the paw but not the tail. Studies of heat and cold sensitivity also show variability depending on the intensity of the stimulus. Deleting Nav1.7, Nav1.8 or Nav1.9 in Nav1.8-positive sensory neurons attenuates responses to slow noxious heat ramps, whilst responses to fast noxious heat ramps are only reduced when Nav1.7 is lost in large diameter sensory neurons. Deleting Nav1.7 from all sensory neurons attenuates responses to noxious cooling but not extreme cold. Finally, circadian rhythms dramatically influence behavioural outcome measures such as von Frey responses, which change by 80% over the day. These observations demonstrate that fully characterising the phenotype of a transgenic mouse strain requires a range of behavioural pain models. Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether.     

Subjects with Knee Osteoarthritis Exhibit Widespread Hyperalgesia to Pressure and Cold

Hyperalgesia to mechanical and thermal stimuli are characteristics of a range of disorders such as tennis elbow, whiplash and fibromyalgia. This study evaluated the presence of local and widespread mechanical and thermal hyperalgesia in individuals with knee osteoarthritis, compared to healthy control subjects. Twenty-three subjects with knee osteoarthritis and 23 healthy controls, matched for age, gender and body mass index, were recruited for the study. Volunteers with any additional chronic pain conditions were excluded. Pain thresholds to pressure, cold and heat were tested at the knee, ipsilateral heel and ipsilateral elbow, in randomized order, using standardised methodology. Significant between-groups differences for pressure pain and cold pain thresholds were found with osteoarthritic subjects demonstrating significantly increased sensitivity to both pressure (p = .018) and cold (p = .003) stimuli, compared with controls. A similar pattern of results extended to the pain-free ipsilateral ankle and elbow indicating widespread pressure and cold hyperalgesia. No significant differences were found between groups for heat pain threshold, although correlations showed that subjects with greater sensitivity to pressure pain were also likely to be more sensitive to both cold pain and heat pain. This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may play a role in ongoing arthritic pain for some patients.     

Sex differences in thermal detection and thermal pain threshold and the thermal grill illusion: a psychophysical study in young volunteers

Background

Sex-related differences in human thermal and pain sensitivity are the subject of controversial discussion. The goal of this study in a large number of subjects was to investigate sex differences in thermal and thermal pain perception and the thermal grill illusion (TGI) as a phenomenon reflecting crosstalk between the thermoreceptive and nociceptive systems. The thermal grill illusion is a sensation of strong, but not necessarily painful, heat often preceded by transient cold upon skin contact with spatially interlaced innocuous warm and cool stimuli.

Methods

The TGI was studied in a group of 78 female and 58 male undergraduate students and was evoked by placing the palm of the right hand on the thermal grill (20/40 °C interleaved stimulus). Sex-related thermal perception was investigated by a retrospective analysis of thermal detection and thermal pain threshold data that had been measured in student laboratory courses over 5 years (776 female and 476 male undergraduate students) using the method of quantitative sensory testing (QST). To analyse correlations between thermal pain sensitivity and the TGI, thermal pain threshold and the TGI were determined in a group of 20 female and 20 male undergraduate students.

Results

The TGI was more pronounced in females than males. Females were more sensitive with respect to thermal detection and thermal pain thresholds. Independent of sex, thermal detection thresholds were dependent on the baseline temperature with a specific progression of an optimum curve for cold detection threshold versus baseline temperature. The distribution of cold pain thresholds was multi-modal and sex-dependent. The more pronounced TGI in females correlated with higher cold sensitivity and cold pain sensitivity in females than in males.

Conclusions

Our finding that thermal detection threshold not only differs between the sexes but is also dependent on the baseline temperature reveals a complex processing of “cold” and “warm” inputs in thermal perception. The results of the TGI experiment support the assumption that sex differences in cold-related thermoreception are responsible for sex differences in the TGI.