UNASSIGNED: In the thermal grill illusion, participants experience a feeling similar to burning pain. The illusion is induced by simultaneously touching warm and cool stimuli in alternating positions. In post-stroke pain, central sensitization is caused by a variety of factors, including damage to the spinothalamic tract and shoulder pain. Because the thermal grill illusion depends on central mechanisms, it has recently been suggested that it may be a useful indicator of central sensitization. Therefore, we hypothesized that post-stroke patients who are more likely to experience central sensitization may also be more likely to experience a thermal grill sensation of pain and discomfort than the likelihood among those who are less likely to experience central sensitization. However, the effects of the thermal grill illusion in post-stroke patients have not yet been reported. In this pilot study, we conducted the thermal grill illusion procedure in post-stroke patients and analyzed the relationship between clinical somatosensory functions and thermal grill sensations. We also conducted brain imaging analysis to identify brain lesion areas that were associated with thermal grill sensations.
UNASSIGNED: Twenty patients (65.7 ± 11.9 years old) with post-stroke patients participated in this study. The thermal grill illusion procedure was performed as follows: patients simultaneously touched eight water-filled copper bars, with the water temperature adjusted to provide alternate warm (40°C) and cold (20°C) stimuli.
UNASSIGNED: Thermal grill sensation of pain and discomfort tended to be associated with the wind-up phenomenon in bedside quantitative sensory testing and thermal grill sensation of discomfort was also related to damage to the thalamic lateral nucleus.
UNASSIGNED: These findings suggest that the thermal grill illusion might measure central sensitization, and that secondary brain hyperactivity might lead to increased thermal grill sensations.

The thermal grill illusion (TGI) describes a peculiar or even painful percept caused by non-noxious, interlaced warm and cold stimuli. It involves the glutamatergic system and is affected in putatively nociplastic syndromes such as fibromyalgia. The glutamatergic system is also involved in wind-up, that is, the increased activation of spinal neurons following repeated noxious stimulation leading to a temporal summation of perceived stimulus intensity. Here we combined both stimulation methods to further investigate whether non-noxious stimuli as employed in the TGI can lead to a similar summation of perceived stimulus intensity. In an experiment using a full crossover within-subjects design, 35 healthy volunteers received repeated stimuli, either in a thermal grill configuration or simply noxious heat. Both modalities were presented as sequences of 1 lead-in contact, followed by 11 consecutive contacts (each between 1.5 and 3 seconds), with either fast repetition (\"wind-up\" condition), or 2 slow-repeating control conditions. The main analyses concerned the relative pre-to-post sequence changes to quantify putatively wind-up-related effects. Pain ratings and skin conductance level (SCL) increased more strongly in \"wind-up\" than in control conditions. Interestingly, wind-up-related effects were of the same magnitude in TGI as compared to the pain control modality. Further, contact-by-contact SCL tracked how the effect emerged over time. These results indicate that although TGI does not involve noxious stimuli it is amenable to temporal summation and wind-up-like processes. Since both phenomena involve the glutamatergic system, the combination of wind-up with the TGI could yield a promising tool for the investigation of chronic pain conditions. PERSPECTIVE: Using thermal stimuli in an experimental protocol to combine 1) the TGI (painful or peculiar percept from simultaneous cold/warm stimulation) and 2) wind-up (increase in stimulus intensity after repeated exposure) holds promise to investigate pain and thermoceptive mechanisms, and chronic pain conditions.

UNASSIGNED: This study aimed to use thermal grill illusion (TGI), an experimental model of pain processing and central mechanisms, to evaluate the perception of TGI-related sensations or pain in patients with chronic lower back pain (CLBP).
UNASSIGNED: The perception of TGI (warmth/heat, cold, unpleasantness, pain, burning, stinging, and prickling) was examined in 66 patients with CLBP and compared with that in 22 healthy participants. The visual analog scale (VAS) scores for CLBP, Oswestry Disability Index (ODI), and 12-Item Short Form Survey (SF-12) scores were obtained from the included patients with CLBP.
UNASSIGNED: The CLBP group showed a less intense perception of TGI for sensations of warmth/heat, unpleasantness, and pain than the control group. The CLBP group felt burning sensations lesser than the control (2.77 vs 4.55, P=0.016). In the CLBP group, there were significant correlations between the ODI and the degree of unpleasantness (r=0.381, P=0.002) and prickling sensation (r=0.263, P=0.033). There were also significant correlations between the mental component score of the SF-12 and the degree of warmth/heat (r=-0.246, P=0.046), unpleasantness (r=-0.292, P=0.017), pain (r=-0.292, P=0.017), and burning sensations (r=-0.280, P=0.023).
UNASSIGNED: Our results may be useful for clinicians to evaluate the effectiveness of drugs or interventions to manage centralized LBP.

Paradoxical heat sensation (PHS) and the thermal grill illusion (TGI) are both related to the perception of warmth or heat from innocuous cold stimuli. Despite being described as similar perceptual phenomena, recent findings suggested that PHS is common in neuropathy and related to sensory loss, while TGI is more frequently observed in healthy individuals. To clarify the relationship between these two phenomena, we conducted a study in a cohort of healthy individuals to investigate the association between PHS and TGI. We examined the somatosensory profiles of 60 healthy participants (34 females, median age 25 years) using the quantitative sensory testing (QST) protocol from the German Research Network on Neuropathic Pain. The number of PHS was measured using a modified thermal sensory limen (TSL) procedure where the skin was transiently pre-warmed, or pre-cooled before the PHS measure. This procedure also included a control condition with a pre-temperature of 32 °C. The number of TGI responses was quantified during simultaneous application of warm and cold innocuous stimuli. All participants had normal thermal and mechanical thresholds compared to the reference values from the QST protocol. Only two participants experienced PHS during the QST procedure. In the modified TSL procedure, we found no statistically significant differences in the number of participants reporting PHS in the control condition (N = 6) vs. pre-warming (N = 3; min = 35.7 °C, max = 43.5 °C) and pre-cooling (N = 4, min = 15.0 °C, max = 28.8 °C) conditions. Fourteen participants experienced TGI, and only one participant reported both TGI and PHS. Individuals with TGI had normal or even increased thermal sensation compared to individuals without TGI. Our findings demonstrate a clear distinction between individuals experiencing PHS or TGI, as there was no overlap observed when using identical warm and cold temperatures that were alternated either temporally or spatially. While PHS was previously related to sensory loss, our study revealed that TGI is associated with normal thermal sensitivity. This suggests that an efficient thermal sensory function is essential in generating the illusory sensation of pain of the TGI.

The thermal grill illusion induces a pain sensation under a spatial display of warmth and coolness of approximately 40 °C; and 20 °C. To realize virtual pain display more universally during the virtual reality experience, we proposed a spatiotemporal control method to realize a variable thermal grill illusion and evaluated the effect of the method. First, we examined whether there was a change in the period until pain occurred due to the spatial temperature distribution of pre-warming and pre-cooling and verified whether the period until pain occurred became shorter as the temperature difference between pre-warming and pre-cooling increased. Next, we examined the effect of the number of grids on the illusion and verified the following facts. In terms of the pain area, the larger the thermal area, the larger the pain area. In terms of the magnitude of the pain, the larger the thermal area, the greater the magnitude of the sensation of pain.

The thermal grill illusion (TGI) is a paradoxical perception of burning heat and pain resulting from the simultaneous application of interlaced warm and cold stimuli to the skin. The TGI is considered a type of chronic centralized pain and has been used to apply nociceptive stimuli without inflicting harm to human participants in the study of pain mechanisms. In addition, the TGI is an interesting phenomenon for researchers, and various topics related to the TGI have been investigated in several studies, which we will review here. According to previous studies, the TGI is generated by supraspinal interactions. To evoke the TGI, cold and warm cutaneous stimuli should be applied within the same dermatome or across dermatomes corresponding to adjacent spinal segments, and a significant difference between cold and warm temperatures is necessary. In addition, due the presence of chronic pain, genetic factors, and sexual differences, the intensity of the TGI can differ. In addition, cold noxious stimulation, topical capsaicin, analgesics, self-touch, and the presence of psychological diseases can decrease the intensity of the TGI. Because the TGI corresponds to chronic centralized pain, we believe that the findings of previous studies can be applied to future studies to identify chronic pain mechanisms and clinical practice for pain management.

Application of spatially interlaced innocuous warm and cool stimuli to the skin elicits illusory pain, known as the thermal grill illusion (TGI). This study aimed to discriminate the underlying mechanisms of central and peripheral neuropathic pain focusing on pain quality, which is considered to indicate the underlying mechanism(s) of pain. We compared pain qualities in central and peripheral neuropathic pain with reference to pain qualities of TGI-induced pain.
Experiment 1:137 healthy participants placed their hand on eight custom-built copper bars for 60 s and their pain quality was assessed by the McGill Pain Questionnaire. Experiment 2: Pain quality was evaluated in patients suffering from central and peripheral neuropathic pain (42 patients with spinal cord injury, 31 patients with stroke, 83 patients with trigeminal neuralgia and 131 patients with postherpetic neuralgia).
Experiment 1: Two components of TGI-induced pain were found using principal component analysis: component 1 included aching, throbbing, heavy and burning pain, component 2 included itching, electrical-shock, numbness, and cold-freezing. Experiment 2: Multiple correspondence analysis (MCA) and cross tabulation analysis revealed specific pain qualities including aching, hot-burning, heavy, cold-freezing, numbness, and electrical-shock pain were associated with central neuropathic pain rather than peripheral neuropathic pain.
We found similar qualities between TGI-induced pain in healthy participants and central neuropathic pain rather than peripheral neuropathic pain. The mechanism of TGI is more similar to the mechanism of central neuropathic pain than that of neuropathic pain.

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.
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.
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.
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.

A new active safety concept that engages the driver\'s psychosensory pain-processing mechanism to automatically trigger vigilance enhancement on-demand was proposed in Chang (2012). This concept is based on the hypothesis that a human\'s pain threshold will decline as he or she becomes drowsy, consequently triggering the vigilance enhancer. The objective of this pilot study was to develop methods to test this hypothesis, the results of which could lead to further refinement of the hypothesis and methods, with the ultimate goal of developing new active safety concepts that exploit the driver\'s endogenous psychosensory pain-processing mechanisms. Preliminary results from a pilot study designed to test this hypothesis were presented in Chang (2016). This article presents further analysis of the pilot study data.
Perceived pain responses of six healthy male participants were measured when their vigilance would be under stress. A time-varying thermal grill illusion (TGI) of pain was created using a custom steering wheel with an array of Peltier elements held in the participant\'s palm. The participant\'s pain responses to the TGI stimulus were recorded while changes in his vigilance were monitored using pre- and post-session Psychomotor Vigilance Task (PVT) tests, in-session Percent Eyelid Closure (PERCLOS), and subjective Karolinska Sleepiness Scale (KSS) ratings. The probability of pain response versus TGI temperature stimulus and vigilance measures were then estimated using logistic regression analysis.
The results indicate that the probability of pain response is correlated with the temperature stimuli and the vigilance state. The pain threshold tends to move up or down versus KSS depending on the participant for high-vigilance conditions, but tends to increase when the participant becomes increasing drowsy in low-vigilance conditions. These results were statistically significant for four of the six study participants.
This limited pilot study observed that one\'s pain threshold may or may not initially decrease as originally hypothesized depending on the participant, but then increases as one becomes drowsier. While not definitive, the methods and results of this study may help to refine our hypotheses and design future studies in pursuit of detector-free on-demand driver vigilance enhancement that exploits our body\'s endogenous alert mechanism.

Simultaneous presentation of alternating innocuous warm and cold stimuli induces in most humans a painful sensation called thermal grill illusion (TGI). Here, pain is elicited although nociceptors are not activated. Upon back-translation of behavioural correlates from humans to animals, we found that neither cats nor rodents show adverse reactions when exposed to TGI stimulation. These results question that a TGI observed as a pain-related change in behaviour can be elicited in animals. While distinct neuronal patterns as previously reported may be measurable in animals upon TGI stimulation, their translational meaning towards the sensation elicited in humans is unclear.