Hot topic: Mapping of the human intranasal mucosal thermal sensitivity: A clinical study on thermal threshold and trigeminal receptors.

INTRODUCTION: The olfactory and trigeminal system are closely interlinked. Existing literature has primarily focused on characterizing trigeminal stimulation through mechanical and chemical stimulation, neglecting thermal stimulation thus far. The present study aimed to characterize the intranasal sensitivity to heat and the expression of trigeminal receptors (transient receptor potential channels, TRP). METHODS: A total of 20 healthy participants (aged 21-27 years, 11 women) were screened for olfactory function and trigeminal sensitivity using several tests. Under endoscopic control, a thermal stimulator was placed in 7 intranasal locations: anterior septum, lateral vestibulum, interior nose tip, lower turbinate, middle septum, middle turbinate, and olfactory cleft to determine the thermal threshold. Nasal swabs were obtained in 3 different locations (anterior septum, middle turbinate, olfactory cleft) to analyze the expression of trigeminal receptors TRP: TRPV1, TRPV3, TRPA1, TRPM8. RESULTS: The thermal threshold differed between locations (p = 0.018), with a trend for a higher threshold at the anterior septum (p = 0.092). There were no differences in quantitative receptor expression (p = 0.46) at the different sites. The highest overall receptor RNA expression was detected for TRPV1 over all sites (p<0.001). The expression of TRPV3 was highest at the anterior septum compared to the middle turbinate or the olfactory cleft. The thermal sensitivity correlated with olfactory sensitivity and results from tests were related to trigeminal function like intensity ratings of ammonium, a questionnaire regarding trigeminal function, nasal patency, and CO2 thresholds. However, no correlation was found between receptor expression and psychophysical measures of trigeminal function. DISCUSSION: This study provided the first insights about intranasal thermal sensitivity and suggested the presence of topographical differences in thermal thresholds. There was no correlation between thermal sensitivity and trigeminal mRNA receptor expression. However, thermal sensitivity was found to be associated with psychophysical measures of trigeminal and olfactory function.

Ion channels of cold transduction and transmission.

Thermosensation requires the activation of a unique collection of ion channels and receptors that work in concert to transmit thermal information. It is widely accepted that transient receptor potential melastatin 8 (TRPM8) activation is required for normal cold sensing; however, recent studies have illuminated major roles for other ion channels in this important somatic sensation. In addition to TRPM8, other TRP channels have been reported to contribute to cold transduction mechanisms in diverse sensory neuron populations, with both leak- and voltage-gated channels being identified for their role in the transmission of cold signals. Whether the same channels that contribute to physiological cold sensing also mediate noxious cold signaling remains unclear; however, recent work has found a conserved role for the kainite receptor, GluK2, in noxious cold sensing across species. Additionally, cold-sensing neurons likely engage in functional crosstalk with nociceptors to give rise to cold pain. This Review will provide an update on our understanding of the relationship between various ion channels in the transduction and transmission of cold and highlight areas where further investigation is required.

Functional relationship between peripheral thermosensation and behavioral thermoregulation.

Thermoregulation is a fundamental mechanism for maintaining homeostasis in living organisms because temperature affects essentially all biochemical and physiological processes. Effector responses to internal and external temperature cues are critical for achieving effective thermoregulation by controlling heat production and dissipation. Thermoregulation can be classified as physiological, which is observed primarily in higher organisms (homeotherms), and behavioral, which manifests as crucial physiological functions that are conserved across many species. Neuronal pathways for physiological thermoregulation are well-characterized, but those associated with behavioral regulation remain unclear. Thermoreceptors, including Transient Receptor Potential (TRP) channels, play pivotal roles in thermoregulation. Mammals have 11 thermosensitive TRP channels, the functions for which have been elucidated through behavioral studies using knockout mice. Behavioral thermoregulation is also observed in ectotherms such as the fruit fly, Drosophila melanogaster. Studies of Drosophila thermoregulation helped elucidate significant roles for thermoreceptors as well as regulatory actions of membrane lipids in modulating the activity of both thermosensitive TRP channels and thermoregulation. This review provides an overview of thermosensitive TRP channel functions in behavioral thermoregulation based on results of studies involving mice or Drosophila melanogaster.

A review of assessment methods for measuring individual differences in oral somatosensory perception.

While taste and smell perception have been thoroughly investigated, our understanding of oral somatosensory perception remains limited. Further, assessing and measuring individual differences in oral somatosensory perception pose notable challenges. This review aimed to evaluate the existing methods to assess oral somatosensory perception by examining and comparing the strengths and limitations of each method. The review highlighted the lack of standardized assessment methods and the various procedures within each method. Tactile sensitivity can be assessed using several methods, but each method measures different tactile dimensions. Further investigations are needed to confirm its correlation with texture sensitivity. In addition, measuring a single textural attribute may not provide an overall representation of texture sensitivity. Thermal sensitivity can be evaluated using thermal-change detection or temperature discrimination tests. The chemesthetic sensitivity tests involve either localized or whole-mouth stimulation tests. The choice of an appropriate method for assessing oral somatosensory sensitivity depends on several factors, including the specific research objectives and the target population. Each method has its unique intended purpose, strengths, and limitations, so no universally superior approach exists. To overcome some of the limitations associated with certain methods, the review offers alternative or complementary approaches that could be considered. Researchers can enhance the comprehensive assessment of oral somatosensory sensitivity by carefully selecting and potentially combining methods. In addition, a standardized protocol remains necessary for each method.

KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures.

Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from KCNQ1-/- mice displayed altered action potential firing properties. Strikingly, only male KCNQ1-/- mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in TRPM8-/- animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, KCNQ1 is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.

Biorealistic Neuronal Temperature-Sensitive Dynamics within Threshold Switching Memristors: Toward Neuromorphic Thermosensation.

Neuromorphic nanoelectronic devices that can emulate the temperature-sensitive dynamics of biological neurons are of great interest for bioinspired robotics and advanced applications such as in silico neuroscience. In this work, we demonstrate the biomimetic thermosensitive properties of two-terminal V3O5 memristive devices and showcase their similarity to the firing characteristics of thermosensitive biological neurons. The temperature-dependent electrical characteristics of V3O5-based memristors are used to understand the spiking response of a simple relaxation oscillator. The temperature-dependent dynamics of these oscillators are then compared with those of biological neurons through numerical simulations of a conductance-based neuron model, the Morris-Lecar neuron model. Finally, we demonstrate a robust neuromorphic thermosensation system inspired by biological thermoreceptors for bioinspired thermal perception and representation. These results not only demonstrate the biorealistic emulative potential of threshold-switching memristors but also establish V3O5 as a functional material for realizing solid-state neurons for neuromorphic computing and sensing applications.

Effective brain connectivity related to non-painful thermal stimuli using EEG.

Understanding the brain response to thermal stimuli is crucial in the sensory experience. This study focuses on non-painful thermal stimuli, which are sensations induced by temperature changes without causing discomfort. These stimuli are transmitted to the central nervous system through specific nerve fibers and are processed in various regions of the brain, including the insular cortex, the prefrontal cortex, and anterior cingulate cortex. Despite the prevalence of studies on painful stimuli, non-painful thermal stimuli have been less explored. This research aims to bridge this gap by investigating brain functional connectivity during the perception of non-painful warm and cold stimuli using electroencephalography (EEG) and the partial directed coherence technique (PDC). Our results demonstrate a clear contrast in the direction of information flow between warm and cold stimuli, particularly in the theta and alpha frequency bands, mainly in frontal and temporal regions. The use of PDC highlights the complexity of brain connectivity during these stimuli and reinforces the existence of different pathways in the brain to process different types of non-painful warm and cold stimuli.

Resting energy expenditure differs among individuals with different levels of perceived thermal sensitivity: A cross-sectional study.

Metabolic rate has been used in thermophysiological models for predicting the thermal response of humans. However, only a few studies have investigated the association between an individual's trait-like thermal sensitivity and resting energy expenditure (REE), which resulted in inconsistent results. This study aimed to explore the association between REE and perceived thermal sensitivity. The REE of healthy adults was measured using an indirect calorimeter, and perceived thermal intolerance and sensation in the body were evaluated using a self-administered questionnaire. In total, 1567 individuals were included in the analysis (women = 68.9%, age = 41.1 ±â€…13.2 years, body mass index = 23.3 ±â€…3.3 kg/m2, REE = 1532.1 ±â€…362.4 kcal/d). More women had high cold intolerance (31.8%) than men (12.7%), and more men had high heat intolerance (23.6%) than women (16.1%). In contrast, more women experienced both cold (53.8%) and heat (40.6%) sensations in the body than men (cold, 29.1%; heat, 27.9%). After adjusting for age, fat-free mass, and fat mass, lower cold intolerance, higher heat intolerance, and heat sensation were associated with increased REE only in men (cold intolerance, P for trend = .001; heat intolerance, P for trend = .037; heat sensation, P = .046), whereas cold sensation was associated with decreased REE only in women (P = .023). These findings suggest a link between the perceived thermal sensitivity and REE levels in healthy individuals.

The comprehensive impact of thermal-PM2.5 interaction on subjective evaluation of urban outdoor space: A pilot study in a cold region of China.

Urban outdoor space has a very important impact on the quality of people's outdoor activities, which has influenced people's health and moods. Its influence is the result of the combined action of various factors. Thermal and air quality environment are important factors affecting the overall comfort of the urban outdoor space. At present, there are few research on interaction with thermal and air quality environment. Therefore, a meteorological measurement and questionnaire survey have been conducted in a representative open space in a campus in Xi'an, China. The following are the research results:(1) Mean physiological equivalent temperature (MPET) is a significant factor affecting thermal sensation vote (TSV) and thermal comfort vote (TCV). PM2.5 has no significant effect on thermal comfort vote (TCV), but it is a considerable factor affecting thermal sensation vote (TSV) when 10.2°C ≤ MPET<21°C (P = 0.023 *). (2) PM2.5 is a significant factor affecting air quality vote (AQV) and breathing comfort vote (BCV).Mean physiological equivalent temperature (MPET) has no significant impact on air quality vote (AQV), but it is a considerable factor affecting breathing comfort vote (BCV) when 10.2°C ≤ MPET<21°C (P = 0.01 **). (3) Mean physiological equivalent temperature (MPET) is a significant factor affecting overall comfort vote (OCV), but PM2.5 is not. In general, When 10.2°C ≤ MPET<21°C (-0.5 < -0.37 ≤ TCV ≤ 0.12 <0.5), the interaction between thermal and PM2.5 environment is significant on thermal sensation vote (TSV) and breathing comfort vote (BCV). This study can provide experimental support for the field of multi-factor interaction, which has shown that improving the thermal environment can better breathing comfort, while reducing PM2.5 concentration can promote thermal comfort. And can also provide reference for the study of human subjective comfort in urban outdoor space in the same latitude of the world.

The temperature sensor TWA1 is required for thermotolerance in Arabidopsis.

Plants exposed to incidences of excessive temperatures activate heat-stress responses to cope with the physiological challenge and stimulate long-term acclimation1,2. The mechanism that senses cellular temperature for inducing thermotolerance is still unclear3. Here we show that TWA1 is a temperature-sensing transcriptional co-regulator that is needed for basal and acquired thermotolerance in Arabidopsis thaliana. At elevated temperatures, TWA1 changes its conformation and allows physical interaction with JASMONATE-ASSOCIATED MYC-LIKE (JAM) transcription factors and TOPLESS (TPL) and TOPLESS-RELATED (TPR) proteins for repressor complex assembly. TWA1 is a predicted intrinsically disordered protein that has a key thermosensory role functioning through an amino-terminal highly variable region. At elevated temperatures, TWA1 accumulates in nuclear subdomains, and physical interactions with JAM2 and TPL appear to be restricted to these nuclear subdomains. The transcriptional upregulation of the heat shock transcription factor A2 (HSFA2) and heat shock proteins depended on TWA1, and TWA1 orthologues provided different temperature thresholds, consistent with the sensor function in early signalling of heat stress. The identification of the plant thermosensors offers a molecular tool for adjusting thermal acclimation responses of crops by breeding and biotechnology, and a sensitive temperature switch for thermogenetics.

Unlocking the therapeutic potential of TRPV3: Insights into thermosensation, channel modulation, and skin homeostasis involving TRPV3.

Recent insights reveal the significant role of TRPV3 in warmth sensation. A novel finding elucidated how thermosensation is affected by TRPV3 membrane abundance that is modulated by the transmembrane protein TMEM79. TRPV3 is a warmth-sensitive ion channel predominantly expressed in epithelial cells, particularly skin keratinocytes. Multiple studies investigated the roles of TRPV3 in cutaneous physiology and pathophysiology. TRPV3 activation by innocuous warm temperatures in keratinocytes highlights its significance in temperature sensation, but whether TRPV3 directly contributes to warmth sensations in vivo remains controversial. This review explores the electrophysiological and structural properties of TRPV3 and how modulators affect its intricate regulatory mechanisms. Moreover, we discuss the multifaceted involvement of TRPV3 in skin physiology and pathology, including barrier formation, hair growth, inflammation, and itching. Finally, we examine the potential of TRPV3 as a therapeutic target for skin diseases and highlight its diverse role in maintaining skin homeostasis.

A brainstem-hypothalamus neuronal circuit reduces feeding upon heat exposure.

Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain's parenchyma and ventricular system3-8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.

Burning Question: How Does Our Brain Process Positive and Negative Cues Associated with Thermosensation?

Whether it is the dramatic suffocating sensation from a heat wave in the summer or the positive reinforcement arising from a hot drink on a cold day; we can certainly agree that our thermal environment underlies our daily rhythms of sensation. Extensive research has focused on deciphering the central circuits responsible for conveying the impact of thermogenesis on mammalian behavior. Here, we revise the recent literature responsible for defining the behavioral correlates that arise from thermogenic fluctuations in mammals. We transition from the physiological significance of thermosensation to the circuitry responsible for the autonomic or behavioral responses associated with it. Subsequently, we delve into the positive and negative valence encoded by thermoregulatory processes. Importantly, we emphasize the crucial junctures where reward, pain, and thermoregulation intersect, unveiling a complex interplay within these neural circuits. Finally, we briefly outline fundamental questions that are pending to be addressed in the field. Fully deciphering the thermoregulatory circuitry in mammals will have far-reaching medical implications. For instance, it may lead to the identification of novel targets to overcome thermal pain or allow the maintenance of our core temperature in prolonged surgeries.

Physiological and perceptual responses to temperature step changes between cold and hot environments.

Objectives. This study explores the effects of temperature steps on thermal responses to understand abrupt temperature shifts faced by heat-exposed workers during winter. Methods. Three temperature step changes with three phases (S20: 20-40-20 °C, S30: 10-40-10 °C, S40: 0-40-0 °C) were conducted. Phase 1 took 30 min, phase 2 took 60 min and phase 3 took 40 min. Eleven participants remained sedentary throughout the experiment, and physiological responses, thermal perception and self-reported health symptoms were recorded. Results. In temperature up steps, steady skin temperature and sweating onset were delayed, and heart rate dropped by 10 bpm from S20 to S40. In temperature down steps to cold conditions, individuals transitioned from thermal comfort to discomfort and eventually cold strain. Blood pressure increased in temperature down steps, correlating with temperature step magnitudes. Thermal responses to temperature steps of equal magnitude but opposite directions were asymmetries, which weakened as step magnitude increased. Thermal perceptions responded faster than physiological changes after temperature steps, while self-reported health symptoms lagged behind physiological responses. Conclusions. These findings contribute to expanding basic data to understand the effects of temperature step magnitude and direction.

Dynamic temperature control in microfluidics for in vivo imaging of cold-sensing in C. elegans.

The ability to perceive temperature is crucial for most animals. It enables them to maintain their body temperature and swiftly react to noxiously cold or hot objects. Caenorhabditis elegans is a powerful genetic model for the study of thermosensation as its simple nervous system is well characterized and its transparent body is suited for in vivo functional imaging of neurons. The behavior triggered by experience-dependent thermosensation has been well studied in C. elegans under temperature-gradient environments. However, how C. elegans senses temperature via its nervous system is not well understood due to the limitations of currently available technologies. One major bottleneck is the difficulty in creating fast temperature changes, especially cold stimuli. Here, we developed a microfluidic-based platform that allowed the in vivo functional imaging of C. elegans responding to well-controlled temporally varying temperature stimulation by rapidly switching fluid streams at different temperatures. We used computational models to enable rational design and optimization of experimental conditions. We validated the design and utility of our system with studies of the functional role of thermosensory neurons. We showed that the responses of PVD polymodal nociceptor neurons observed in previous studies can be recapitulated. Further, we highlighted how this platform may be used to dissect neuronal circuits with an example of activity recording in PVC interneurons. Both of these neuron types show sensitization phenotypes. We envision that both the engineered system and the findings in this work will spur further studies of molecular and cellular mechanisms underlying cold-sensing through the nervous system.

Touchless Thermosensation Enabled by Flexible Infrared Photothermoelectric Detector for Temperature Prewarning Function of Electronic Skin.

Artificial skin, endowed with the capability to perceive thermal stimuli without physical contact, will bring innovative interactive experiences into smart robotics and augmented reality. The implementation of touchless thermosensation, responding to both hot and cold stimuli, relies on the construction of a flexible infrared detector operating in the long-wavelength infrared range to capture the spontaneous thermal radiation. This imposes rigorous requirements on the photodetection performance and mechanical flexibility of the detector. Herein, a flexible and wearable infrared detector is presented, on basis of the photothermoelectric coupling of the tellurium-based thermoelectric multilayer film and the infrared-absorbing polyimide substrate. By suppressing the optical reflection loss and aligning the destructive interference position with the absorption peak of polyimide, the fabricated thermopile detector exhibits high sensitivity to the thermal radiation over a broad source temperature range from -50 to 110 °C, even capable of resolving 0.05 °C temperature change. Spatially resolved radiation distribution sensing is also achieved by constructing an integrated thermopile array. Furthermore, an established temperature prewarning system is demonstrated for soft robotic gripper, enabling the identification of noxious thermal stimuli in a contactless manner. A feasible strategy is offered here to integrate the infrared detection technique into the sensory modality of electronic skin.

Plant thermosensors.

Plants dynamically regulate their genes expression and physiological outputs to adapt to changing temperatures. The underlying molecular mechanisms have been extensively studied in diverse plants and in multiple dimensions. However, the question of exactly how temperature is detected at molecular level to transform the physical information into recognizable intracellular signals remains continues to be one of the undetermined occurrences in plant science. Recent studies have provided the physical and biochemical mechanistic breakthrough of how temperature changes can influence molecular thermodynamically stability, thus changing molecular structures, activities, interaction and signaling transduction. In this review, we focus on the thermosensing mechanisms of recognized and potential plant thermosensors, to describe the multi-level thermal input system in plants. We also consider the attributes of a thermosensor on the basis of thermal-triggered changes in function, structure, and physical parameters. This study thus provides a reference for discovering more plant thermosensors and elucidating plant thermal adaptive mechanisms.

Separation of Oral Cooling and Warming Requires TRPM8.

Cooling sensations arise inside the mouth during ingestive and homeostasis behaviors. Oral presence of cooling temperature engages the cold and menthol receptor TRPM8 (transient receptor potential melastatin 8) on trigeminal afferents. Yet, how TRPM8 influences brain and behavioral responses to oral temperature is undefined. Here we used in vivo neurophysiology to record action potentials stimulated by cooling and warming of oral tissues from trigeminal nucleus caudalis neurons in female and male wild-type and TRPM8 gene deficient mice. Using these lines, we also measured orobehavioral licking responses to cool and warm water in a novel, temperature-controlled fluid choice test. Capture of antidromic electrophysiological responses to thalamic stimulation identified that wild-type central trigeminal neurons showed diverse responses to oral cooling. Some neurons displayed relatively strong excitation to cold <10°C (COLD neurons) while others responded to only a segment of mild cool temperatures below 30°C (COOL neurons). Notably, TRPM8 deficient mice retained COLD-type but lacked COOL cells. This deficit impaired population responses to mild cooling temperatures below 30°C and allowed warmth-like (≥35°C) neural activity to pervade the normally innocuous cool temperature range, predicting TRPM8 deficient mice would show anomalously similar orobehavioral responses to warm and cool temperatures. Accordingly, TRPM8 deficient mice avoided both warm (35°C) and mild cool (≤30°C) water and sought colder temperatures in fluid licking tests, whereas control mice avoided warm but were indifferent to mild cool and colder water. Results imply TRPM8 input separates cool from warm temperature sensing and suggest other thermoreceptors also participate in oral cooling sensation.

Thermal sensation prediction model for high-speed train occupants based on skin temperatures and skin wettedness.

Passenger thermal comfort in high-speed train (HST) carriages presents unique challenges due to factors such as extensive operational areas, longer travel durations, larger spaces, and higher passenger capacities. This study aims to propose a new prediction model to better understand and address thermal comfort in HST carriages. The proposed prediction model incorporates skin wettedness, vertical skin temperature difference (ΔTd), and skin temperature as parameters to predict the thermal sensation vote (TSV) of HST passengers. The experiments were conducted with 65 subjects, evenly distributed throughout the HST compartment. Thermal environmental conditions and physiological signals were measured to capture the subjects' thermal responses. The study also investigated regional and overall thermal sensations experienced by the subjects. Results revealed significant regional differences in skin temperature between upper and lower body parts. By analyzing data from 45 subjects, We analyzed the effect of 25 variables on TSV by partial least squares (PLS), from which we singled out 3 key factors. And the optimal multiple regression equation was derived to predict the TSV of HST occupants. Validation with an additional 20 subjects demonstrated a strong linear correlation (0.965) between the actual TSV and the predicted values, confirming the feasibility and accuracy of the developed prediction model. By integrating skin wettedness and ΔTd with skin temperature, the model provides a comprehensive approach to predicting thermal comfort in HST environments. This research contributes to advancing thermal comfort analysis in HST and offers valuable insights for optimizing HST system design and operation to meet passengers' comfort requirements.