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.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

ABSTRACT: The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Modality-Specific Modulation of Temperature Representations in the Spinal Cord after Injury.

Different types of tissue injury, such as inflammatory and neuropathic conditions, cause modality-specific alternations on temperature perception. There are profound changes in peripheral sensory neurons after injury, but how patterned neuronal activities in the CNS encode injury-induced sensitization to temperature stimuli is largely unknown. Using in vivo calcium imaging and mouse genetics, we show that formalin- and prostaglandin E2-induced inflammation dramatically increase spinal responses to heating and decrease responses to cooling in male and female mice. The reduction of cold response is largely eliminated on ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from the hyperactive heat inputs in the spinal cord. Interestingly, chemotherapy medication oxaliplatin can rapidly increase spinal responses to cooling and suppress responses to heating. Together, our results suggest a push-pull mechanism in processing cold and heat inputs and reveal a synergic mechanism to shift thermosensation after injury.SIGNIFICANCE STATEMENT In this paper, we combine our novel in vivo spinal cord two-photon calcium imaging, mouse genetics, and persistent pain models to study how tissue injury alters the sensation of temperature. We discover modality-specific changes of spinal temperature responses in different models of injury. Chemotherapy medication oxaliplatin leads to cold hypersensitivity and heat hyposensitivity. By contrast, inflammation increases heat sensitivity and decreases cold sensitivity. This decrease in cold sensitivity results from the stronger crossover inhibition from the hyperactive heat inputs. Our work reveals the bidirectional change of thermosensitivity by injury and suggests that the crossover inhibitory circuit underlies the shifted thermosensation, providing a mechanism to the biased perception toward a unique thermal modality that was observed clinically in chronic pain patients.

Cold pain sensitivity is associated with single-nucleotide polymorphisms of PAR2/F2RL1 and TRPM8.

Pain sensitivity differs individually, but the mechanisms and genetic factors that underlie these differences are not fully understood. To investigate genetic factors that are involved in sensing cold pain, we applied a cold-induced pain test and evaluated protease-activated receptor 2 (PAR2/F2RL1) and transient receptor potential melastatin 8 (TRPM8), which are related to pain. We statistically investigated the associations between genetic polymorphisms and cold pain sensitivity in 461 healthy patients who were scheduled to undergo cosmetic orthognathic surgery for mandibular prognathism. We found an association between cold pain sensitivity and the rs2243057 polymorphism of the PAR2 gene. We also found a significant association between cold pain sensitivity and the rs12992084 polymorphism of the TRPM8 gene. Carriers of the minor A allele of the rs2243057 polymorphism of PAR2 and minor C allele of the rs12992084 polymorphism of TRPM8 exhibited a longer latency to pain perception in the cold-induced pain test, reflecting a decrease in cold pain sensitivity. These results suggest that genetic polymorphisms of both PAR2 and TRPM8 are involved in individual differences in cold pain sensitivity.

A Systematic Review Into the Influence of Temperature on Fibromyalgia Pain: Meteorological Studies and Quantitative Sensory Testing.

Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies. The review was registered with Prospero: ID-CRD42020167687, and followed PRISMA guidance. Databases interrogated were: MEDLINE (via OVID), EMBASE, PubMed, Web of Science, ScienceDirect, CINAHL, and ProQuest (Feb'20). Exclusion criteria were: age <18, animal studies, non-English, and noncontrolled articles. Thirteen studies pertaining to ambient temperature and FMS pain were identified; 9 of these found no uniform relationship. Thirty-five QST studies were identified, 17 of which assessed cold pain thresholds (CPTs). All studies showed numerically reduced CPTs in patients, ranging from 10.9°C to 26.3°C versus 5.9°C to 13.5°C in controls; this was statistically significant in 14/17. Other thermal thresholds were often abnormal. We conclude that the literature provides consistent evidence for an abnormal sensitization of FMS patients' temperature-sensation systems. Additional work is required to elucidate the factors that determine why a subgroup of patients perceive low ambient temperatures as painful, and to characterize that group. PERSPECTIVE: Patients often report increased pain with changes in ambient temperature; even disabling, extreme temperature sensitivity in winter. Understanding this phenomenon may help clinicians provide reassurance and advice to patients and may guide research into the everyday impact of such hypersensitivity, whilst directing future work into the pathophysiology of FMS.

Characterization of PC12 Cell Subclones with Different Sensitivities to Programmed Thermal Stimulation.

Neuritogenesis is the process underling nervous system regeneration; however, optimal extracellular signals that can promote neuronal regenerative activities require further investigation. Previously, we developed a novel method for inducing neuronal differentiation in rat PC12 cells using temperature-controlled repeated thermal stimulation (TRTS) with a heating plate. Based on neurogenic sensitivity to TRTS, PC12 cells were classified as either hyper- or hyposensitive. In this study, we aimed to investigate the mechanism of hyposensitivity by establishing two PC12-derived subclones according to TRTS sensitivity during differentiation: PC12-P1F1, a hypersensitive subclone, and PC12-P1D10, a hyposensitive subclone. To characterize these subclones, cell size and neuritogenesis were evaluated in subclones treated with nerve growth factor (NGF), bone morphogenetic protein (BMP), or various TRTS. No significant differences in cell size were observed among the parental cells and subclones. BMP4- or TRTS-induced neuritogenesis was increased in PC12-P1F1 cells compared to that in the parental cells, while no neuritogenesis was observed in PC12-P1D10 cells. In contrast, NGF-induced neuritogenesis was observed in all three cell lines. Furthermore, a BMP inhibitor, LDN-193189, considerably inhibited TRTS-induced neuritogenesis. These results suggest that the BMP pathway might be required for TRTS-induced neuritogenesis, demonstrating the useful aspects of these novel subclones for TRTS research.

A mathematical model analyzing temperature threshold dependence in cold sensitive neurons.

Here we examine a class of neurons that have been recently explored, the somatosensory neuronal subclass of cold thermosensors. We create a mathematical model of a cold sensing neuron that has been formulated to understand the variety of ionic channels involved. In particular this model showcases the role of TRPM8 and voltage gated potassium channels in setting the temperature dependent activation and inactivation threshold level. Bifurcation analysis of the model demonstrates that a Hodgkin-Huxley type model with additional TRPM8 channels is sufficient to replicate observable experimental features of when different threshold level cold thermosensors turn on. Additionally, our analysis gives insight into what is happening at the temperature levels at which these neurons shut off and the role sodium and leak currents may have in this. This type of model construction and analysis provides a framework moving forward that will help tackle less well understood neuronal classes and their important ionic channels.

Occurrence of cold sensitivity in carpal tunnel syndrome and its effects on surgical outcome following open carpal tunnel release.

Cold sensitivity is common following nerve injuries in the upper extremity, but is less well studied in carpal tunnel syndrome (CTS). We investigated cold sensitivity in CTS and its effects on surgical outcome. A search of the Swedish National Registry for Hand Surgery (HAKIR) for open carpal tunnel releases (OCTR) from 2010-2016 identified 10,746 cases. Symptom severity questionnaires (HQ-8; HAKIR questionnaire 8, eight Likert-scale items scored 0-100, one item on cold sensitivity) and QuickDASH scores before and after surgery were collected. Patient mean age was 56 ± SD 16 years, and 7,150/10,746 (67%) were women. Patients with severe cold sensitivity (defined as cold intolerance symptom severity score > 70; n = 951), scored significantly higher on QuickDASH at all time points compared to those with mild cold sensitivity (cold intolerance symptom severity scores ≤ 30, n = 1,532); preoperatively 64 [50-75] vs. 40 [25-55], at three months 32 [14-52] vs. 18 [9-32] and at 12 months 25 [7-50] vs. 9 [2-23]; all p < 0.0001. Severe cold sensitivity predicted higher postoperative QuickDASH scores at three [12.9 points (95% CI 10.2-15.6; p < 0.0001)] and at 12 months [14.8 points (11.3-18.4; p < 0.0001)] compared to mild cold sensitivity, and adjustment for a concomitant condition in the hand/arm, including ulnar nerve compression, did not influence the results. Cold sensitivity improves after OCTR. A higher preoperative degree of cold sensitivity is associated with more preoperative and postoperative disability and symptoms than a lower degree of cold sensitivity, but with the same improvement in QuickDASH score.

Dogs can sense weak thermal radiation.

The dog rhinarium (naked and often moist skin on the nose-tip) is prominent and richly innervated, suggesting a sensory function. Compared to nose-tips of herbivorous artio- and perissodactyla, carnivoran rhinaria are considerably colder. We hypothesized that this coldness makes the dog rhinarium particularly sensitive to radiating heat. We trained three dogs to distinguish between two distant objects based on radiating heat; the neutral object was about ambient temperature, the warm object was about the same surface temperature as a furry mammal. In addition, we employed functional magnetic resonance imaging on 13 awake dogs, comparing the responses to heat stimuli of about the same temperatures as in the behavioural experiment. The warm stimulus elicited increased neural response in the left somatosensory association cortex. Our results demonstrate a hitherto undiscovered sensory modality in a carnivoran species.

Analysis of the effects of subthalamic nucleus deep brain stimulation on somatosensation in Parkinson's disease patients.

OBJECTIVE: Despite the subthalamic nucleus (STN) deep brain stimulation (DBS) is a treatment commonly used to ameliorate the motor symptoms of Parkinson's disease (PD), its effects on somatosensation is unclear. The purpose of this study was to investigate the potential effects of DBS on temperature, proprioceptive, tactile, exteroceptive, pain and cortical sensations, and odor identification in PD patients. METHODS: The study included 14 patients (with a mean age of 59.78 ± 11.03 years; range, 44-70 years) with idiopathic PD who underwent DBS surgery for movement disorders caused by PD at the same Neurosurgery Department. All patients were tested while DBS was turned on (DBS-ON) and off (DBS-OFF). To clearly observe the effect of removing stimulation off, DBS devices were turned off by experimental clinical personnel for a minimum duration of 30 min prior to examination. Temperature, proprioceptive, tactile, exteroceptive, pain and cortical sensations, and odor identification were examined. RESULTS: We found that two-point discrimination was significantly lower during DBS-ON than DBS-OFF (p = 0.031). Tactile sensation and kinesthesia deviation degree were lower during DBS-ON than DBS-OFF, but were non-significant (p > 0.05). The number of correct answers on an assessment of graphesthesia was higher during DBS-ON, but was non-significant as well (p > 0.05). Odor identification was better during DBS-OFF. CONCLUSIONS: DBS may have an effective role to improve somatosensation and DBS-related benefits may not be explained by improvements in motor function alone, but rather by enhanced somatosensory processing. Further studies with larger study groups are needed.

Correcting the Error in Measuring Radiation Received by a Person: Introducing Cylindrical Radiometers.

Most human energy budget models consider a person to be approximately cylindrical in shape when estimating or measuring the amount of radiation that they receive in a given environment. Yet, the most commonly used instrument for measuring the amount of radiation received by a person is the globe thermometer. The spherical shape of this instrument was designed to be used indoors where radiation is received approximately equally from all directions. But in outdoor environments, radiation can be strongly directional, making the sphere an inappropriate shape. The international standard for measuring radiation received by a person, the Integral Radiation Measurement (IRM) method, yields a measure of the Mean Radiant Temperature (Tmrt). This method uses radiometers oriented in the four cardinal directions, plus up and down. However, this setup essentially estimates the amount of energy received by a square peg, not a cylinder. This paper identifies the errors introduced by both the sphere and the peg, and introduces a set of two new instrument that can be used to directly measure the amount of radiation received by a vertical cylinder in outdoor environments. The Cylindrical Pyranometer measures the amount of solar radiation received by a vertical cylinder, and the Cylindrical Pyrgeometer measures the amount of terrestrial radiation received. While the globe thermometer is still valid for use in indoor environments, these two new instruments should become the standard for measuring radiation received by people in outdoor environments.

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain.

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain-relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.

Thermosensory mapping of skin wetness sensitivity across the body of young males and females at rest and following maximal incremental running.

KEY POINTS: Humans lack skin receptors for wetness (i.e. hygroreceptors), yet we present a remarkable wetness sensitivity. Afferent inputs from skin cold-sensitive thermoreceptors are key for sensing wetness; yet, it is unknown whether males and females differ in their wetness sensitivity across their body and whether high intensity exercise modulates this sensitivity. We mapped sensitivity to cold, neutral and warm wetness across five body regions and show that females are more sensitive to skin wetness than males, and that this difference is greater for cold than warm wetness sensitivity. We also show that a single bout of maximal exercise reduced the sensitivity to skin wetness (i.e. hygro-hypoesthesia) of both sexes as a result of concurrent decreases in thermal sensitivity. These novel findings clarify the physiological mechanisms underpinning this fundamental human sensory experience. In addition, they indicate sex differences in thermoregulatory responses and will inform the design of more effective sport and protective clothing, as well as thermoregulatory models. ABSTRACT: Humans lack skin hygroreceptors and we rely on integrating cold and tactile inputs from A-type skin nerve fibres to sense wetness. Yet, it is unknown whether sex and exercise independently modulate skin wetness sensitivity across the body. We mapped local sensitivity to cold, neutral and warm wetness of the forehead, neck, underarm, lower back and dorsal foot in 10 males (27.8 ± 2.7 years; 1.92 ± 0.1 m2 body surface area) and 10 females (25.4 ± 3.9 years; 1.68 ± 0.1 m2 body surface area), at rest and post maximal incremental running. Participants underwent our quantitative sensory test where they reported the magnitude of thermal and wetness perceptions (visual analogue scale) resulting from the application of a cold (5°C below skin temperature) wet (0.8 mL of water), neutral wet and warm wet (5°C above skin temperature) thermal probe (1.32 cm2 ) to five skin sites. We found that: (i) females were ∼14% to ∼17% more sensitive to cold-wetness than males, yet both sexes were as sensitive to neutral- and warm-wetness; (ii) regional differences were present for cold-wetness only, and these followed a craniocaudal increase that was more pronounced in males (i.e. the foot was ∼31% more sensitive than the forehead); and (iii) maximal exercise reduced cold-wetness sensitivity over specific regions in males (i.e. ∼40% decrease in foot sensitivity), and also induced a generalized reduction in warm-wetness sensitivity in both sexes (i.e. ∼4% to ∼6%). For the first time, we show that females are more sensitive to cold wetness than males and that maximal exercise induce hygro-hypoesthesia. These novel findings expand our knowledge on sex differences in thermoregulatory physiology.

Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol and mustard oil.

KEY POINTS: Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range. Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol, and/or mustard oil (allyl isothiocyanate) at concentrations found in foods and spices. There is significant but incomplete overlap between afferent trigeminal neurons that respond to oral thermal stimulation and to the above chemesthetic compounds. Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses. ABSTRACT: When consumed with foods, mint, mustard, and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants - menthol, allyl isothiocyanate (AITC), and capsaicin, respectively - at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ∼10% of imaged neurons. We categorized them into three distinct classes: cool-responsive and warm-responsive thermosensors, and nociceptors (responsive only to temperatures ≥43-45 °C). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm-responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.

Is quantitative sensory testing helpful in the management of oxaliplatin neuropathy? a two-year clinical study.

PURPOSE: To better understand how quantitative sensory testing could help the clinician in the management of oxaliplatin-induced peripheral neuropathy in terms of earlier and more reliable detection, we conducted a two-year prospective study. METHODS: Thermal sensory assessment, tactile sensory assessment, neuropathic pain assessment and adverse events gradation (NCI-CTC) were performed during treatment and 6 months after treatment completion. RESULTS: 35 patients were enrolled and followed-up during one year. Cold and Warm Detection Thresholds were higher 6 months after treatment completion than at enrollment. Mechanical detection thresholds didn't change significantly. Neurotoxicity was mostly grade-1, only 18% grade-2 and no grade-3. Grade-2 patients received lower oxaliplatin cumulative dose than grade-1, which reveals effective dose adaptation and grade-2 patients were more likely to develop painful neuropathy. CONCLUSION: Thermal thresholds impairment emerges too late to help the clinician in the prophylaxis of neuropathy. Management of OXA-treatment based on NCI-CTC, as currently recommended, remains the best way to detect neuropathy and ensure treatment adaptation.

Sex difference in thermal preference of adult mice does not depend on presence of the gonads.

BACKGROUND: The thermoneutral zone (TNZ) is a species-specific range of ambient temperature (T a), at which mammals can maintain a constant body temperature with the lowest metabolic rate. The TNZ for an adult mouse is between 26 and 34 °C. Interestingly, female mice prefer a higher T a than male mice although the underlying mechanism for this sex difference is unknown. Here, we tested whether gonadal hormones are dominant factors controlling temperature preference in male and female mice. METHODS: We performed a temperature preference test in which 10-week-old gonadectomized and sham-operated male and female C57BL/6J mice were allowed to choose to reside at the thermoneutral cage of 29 °C or an experimental cage of 26, 29, or 32 °C. RESULTS: All mice preferred a T a higher than 26 °C, especially in the inactive phase. Choosing between 29 and 32 °C, female mice resided more at 32 °C while male mice had no preference between the temperatures. Hence, the preferred T a for female mice was significantly higher (0.9 ± 0.2 °C) than that for male mice. However, gonadectomy did not influence the T a preference. CONCLUSIONS: Female mice prefer a warmer environment than male mice, a difference not affected by gonadectomy. This suggests that thermal-sensing mechanisms may be influenced by sex-specific pathways other than gonadal factors or that the thermoregulatory set point has already been determined prior to puberty.

The Status of Affected Infraorbital Nerve and Inferior Alveolar Nerve in Patients With Jaw Fibrous Dysplasia: A Clinical and Radiographic Evaluation.

The affected infraorbital nerve (IFBN) and inferior alveolar nerve (IFAN) status in patients with jaw fibrous dysplasia has not been definitely depicted. In this study, the authors try to explore the status of affected IFBN and IFAN in patients with jaw fibrous dysplasia. Ten patients with jaw fibrous dysplasia were included in this study. The complaints of numbness in the IFBA and IFAN innervated area were asked and recorded, and careful clinical examination was performed to evaluate the touch sense, pain sense, pressure sense, and temperature sense in the IFBA and IFAN innervated areas. Computed tomography scans also were performed to evaluate the imaging characteristics of affected IFBA and IFAN. The results showed that 1 patient with maxillary lesion showed complaints of slight numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense. In addition, 1 patient with mandibular lesion showed relative obvious complaints of numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense and temperature sense, but not serious. All other patients exhibited no numbness in the IFBA and IFAN innervated area. Although the position and morphology changed in some patients, all neural canal of affected IFBA or IFAN existed and showed no invasion of lesion. Taking these findings together, it further confirmed that evaluation of the function of IFBAN and IFAN is necessary for patients with jaw fibrous dysplasia, and the affected IFBAN and IFAN may should be reserved in most patients with jaw fibrous dysplasia when resecting or recontouring the lesion.

Pathophysiology of pruritus in primary localized cutaneous amyloidosis.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic dermatosis prevalent among Southern Chinese and South American populations. Pruritus is frequently present and can be debilitating; its pathophysiology is largely unknown. OBJECTIVES: To investigate if small-fibre neuropathy (SFN), which results in a reduction of intraepidermal nerve fibres (IENF) and abnormalities in quantitative thermal sensory testing (QST), is present in PLCA. METHODS: Twenty Chinese patients (10 men) and 20 ethnicity-, sex- and age-matched controls underwent QST assessments. The patients' warm detection threshold (WDT) and heat pain threshold at the typical lesional sites were determined. Serum interleukin (IL)-31 levels were measured. Lesional biopsies were stained for IENF, IL-31 and its receptor's subunits [IL-31RA and oncostatin M receptor-ß (OSMRß)], and nerve growth factor (NGF) and its receptor [tropomyosin receptor kinase A (TrkA)], and were compared with normal skin obtained from archival paraffin-embedded specimens. RESULTS: WDT was significantly higher in patients at all sites and correlated with itch scores (r = 0·59; P < 0·01). Patient biopsies revealed lower IENF counts (P < 0·01 using protein gene product 9.5, ß3-tubulin and Neurofilament 200 stains) and increased epidermal expression of OSMRß (P < 0·01) and IL-31RA (P < 0·01). Cutaneous IL-31, NGF and TrkA stains were not significantly increased in patients. Serum IL-31 was not significantly higher in patients. CONCLUSIONS: SFN is present in PLCA. Pruritus in PLCA is likely associated with hypersensitivity of cutaneous nerve fibres, which may be related to an increased expression of epidermal IL-31 receptors. Targeting IL-31 receptors is therefore a potential therapeutic approach.

Investigation of gender difference in human response to temperature step changes.

The purpose of this study was to examine gender difference in human response to temperature step changes. A total of three step-change conditions (S5: 32 °C-37 °C-32 °C, S11: 26 °C-37 °C-26 °C, and S15: 22 °C-37 °C-22 °C) were designed and a laboratory experiment with 12 males and 12 females was performed. Results of this study support our hypothesis that females differ from males in human response to sudden temperature changes from the perspectives of psychology, physiology and biomarkers. Females are more prone to show thermal dissatisfaction to cool environments while males are more likely to feel thermal discomfort in warm environments. It is logical that men have a stronger thermoregulation ability than women as male skin temperature change amplitude is smaller while the time to be stable for skin temperature is shorter than that of females after both up-steps and down-steps. In S15, males witnessed a more intensive decrease in RMSSD while females underwent a remarkable instant reduce in oral temperatures after the up-step. Marginal significance was observed in male IL-6 before and after the up-step in S15 while female IL-6 prominently increased after the down-step in S15.

Sensitivity of the Nipple-Areola Complex and Sexual Function Following Reduction Mammaplasty.

BACKGROUND: The sensitivity of the nipple-areola complex (NAC) is very relevant to female sexuality. OBJECTIVE: To evaluate NAC sensitivity and sexual function after breast reduction, and to assess whether altered NAC sensitivity is related to sexual dysfunction. METHODS: The study included 80 patients, who were allocated to a control group with eutrophic breasts (CG, n = 20), a hypertrophy group without surgery (HG, n = 20), or a mammaplasty group (MG, n = 40). The MG was assessed preoperatively and 6 months postoperatively. The HG and CG were evaluated once. NAC sensitivity was assessed for touch, temperature, vibration, and pressure in four areola quadrants and the nipple. Sexual function was assessed with the Brazilian version of the Female Sexual Function Index, which has six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) and a total score that indicates the presence or absence of sexual dysfunction. RESULTS: Compared to the CG, the MG had worse sensitivity to temperature and pressure in the nipple and areola medial quadrants postoperatively (P < 0.01). Compared to their preoperative assessment, the MG had reduced temperature and pressure sensitivity in the nipple and areola medial quadrants postoperatively (P < 0.05). Compared to the CG and HG, patients in the MG had higher postoperative scores of excitation (P = 0.0001), lubrication (P = 0.0004), orgasm (P < 0.0001), and satisfaction (P < 0.0001). There was an association between sexual dysfunction and low NAC sensitivity to temperature and vibration (P ≤ 0.041) in the MG's preoperative and postoperative scores, and to touch, temperature, and pressure across all three groups. CONCLUSIONS: Breast reduction with a superomedial pedicle reduced NAC sensitivity but did not interfere with sexual function.