Cold Thresholds Research Articles

Underlying mechanism of diurnal change in thermal sensation response at high relative humidity.

Diurnal changes in physiological and behavioral responses to constant relative humidity (RH) were investigated in summer to validate a hypothesis that thermal sensation responses (TSR) vary with the diurnal cycle while maintained at stable RH's of 60, 70, or 80%. Seven lightly clothed male subjects were exposed to one of three RH while air temperature (Ta) was held at 28°C from 9:00-18:30. Mean skin temperature (T‾sk) and tympanic temperature (Tty) were monitored at 2-min intervals throughout the experimental period. Cutaneous warm and cool sensation thresholds and stratum corneum water content (SCWC) on the anterior forearm, posterior forearm, and anterior thigh, finger blood flow rate (SkBF) were measured by a thermal stimulator controlled by a Peltier element (Intercross-230; Intercross, Co., Tokyo, Japan), a water content of stratum corneum monitor (Corneometer CM825 & MPA 5; Integral Co., Tokyo, Japan), and a laser flowmeter (ALF21; Advance Co., Tokyo, Japan), accordingly at the end of three periods: 9:30-10:30, 13:30-14:30, and 17:30-18:30. The TSR and the thermal comfort response were also recorded using subjective scales of thermal sensation and comfort thresholds at the end of three periods. The Tty and mean skin temperature (T‾sk) remained unchanged during the day under all RH conditions. Temperature difference between warm and cold sensation thresholds and SkBF decreased slightly towards the evening under all RH conditions whereas SCWC increased from the morning to the evening at 60% and 80% RH. Behaviorally, the subjects responded more than "slightly warm" at 70%, and 80% RH, and then the TSR changed significantly (p<0.05) to less than "slightly warm" in the evening, although T̅sk remained unchanged at 34.0°C. The results from the previous study in winter was reconfirmed, and the data verify the hypothesis that TSR changes diurnally even though subjects are exposed to a constant and high RH's and stable Ta. It was confirmed in summertime as previously shown in wintertime that the combined reduction in SkBF to increases SCWC when exposed to high RH explains the altered TSR although Ta are unchanged.

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Damage to small nociceptive fibres may contribute to painful diabetic neuropathy. We aimed to compare large and small nerve fibre measurements together with skin biopsy and corneal confocal microscopy in patients with type 1 diabetes and painful or painless diabetic neuropathy. We have assessed the McGill pain questionnaire, neuropathy disability score, vibration perception threshold, warm and cold sensation thresholds, electrophysiology, corneal confocal microscopy and skin biopsy in participants with type 1 diabetes and painful (n=41) or painless (n=50) diabetic neuropathy and control subjects (n=50). The duration of diabetes, body mass index, glycated haemoglobin (HbA1c), blood pressure and lipid profile did not differ between subjects with painful and painless neuropathy. Neuropathy disability score and vibration perception threshold were higher and sural nerve conduction velocity was lower, but sural nerve amplitude, peroneal nerve amplitude and conduction velocity and cold and warm sensation thresholds did not differ between patients with painful compared to painless diabetic neuropathy. However, intraepidermal nerve fibre density, corneal nerve fibre density, corneal nerve branch density and corneal nerve fibre length were significantly lower in subjects with painful compared to painless diabetic neuropathy. There is evidence of more severe neuropathy, particularly small fibre damage in the skin and cornea, of patients with painful compared to painless diabetic neuropathy.

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Thermal limits for flight activity of field-collected Culicoides in the United Kingdom defined under laboratory conditions

BackgroundCulicoides biting midges (Diptera: Ceratopogonidae) are biological vectors of internationally important arboviruses and inflict biting nuisance on humans, companion animals and livestock. In temperate regions, transmission of arboviruses is limited by temperature thresholds, in both replication and dissemination of arboviruses within the vector and in the flight activity of adult Culicoides. This study aims to determine the cold-temperature thresholds for flight activity of Culicoides from the UK under laboratory conditions.MethodsOver 18,000 Culicoides adults were collected from the field using 4 W down-draught miniature ultraviolet Centers for Disease Control traps. Populations of Culicoides were sampled at three different geographical locations within the UK during the summer months and again in the autumn at one geographical location. Activity at constant temperatures was assessed using a bioassay that detected movement of adult Culicoides towards an ultraviolet light source over a 24-h period.ResultsThe proportion of active adult Culicoides increased with temperature but cold temperature thresholds for activity varied significantly according to collection season and location. Populations dominated by the subgenus Avaritia collected in South East England had a lower activity threshold temperature in the autumn (4 °C) compared with populations collected in the summer (10 °C). Within the subgenus Avaritia, Culicoides scoticus was significantly more active across all temperatures tested than Culicoides obsoletus within the experimental setup. Populations of Culicoides impunctatus collected in the North East of England were only active once temperatures reached 14 °C. Preliminary data suggested flight activity of the subgenus Avaritia does not differ between populations in South East England and those in the Scottish Borders.ConclusionsThese findings demonstrate seasonal changes in temperature thresholds for flight and across different populations of Culicoides. These data, alongside that defining thresholds for virus replication within Culicoides, provide a primary tool for risk assessment of arbovirus transmission in temperate regions. In addition, the study also provides a comparison with thermal limits derived directly from light-suction trapping data, which is currently used as the main method to define adult Culicoides activity during surveillance.Graphical

Patients with Minimal Hepatic Encephalopathy Show Altered Thermal Sensitivity and Autonomic Function.

Cirrhotic patients may experience alterations in the peripheral nervous system and in somatosensory perception. Impairment of the somatosensory system could contribute to cognitive and motor alterations characteristic of minimal hepatic encephalopathy (MHE), which affects up to 40% of cirrhotic patients. We assessed the relationship between MHE and alterations in thermal, vibration, and/or heat pain sensitivity in 58 cirrhotic patients (38 without and 20 with MHE according to Psychometric Hepatic Encephalopathy Score) and 39 controls. All participants underwent attention and coordination tests, a nerve conduction study, autonomic function testing, and evaluation of sensory thresholds (vibration, cooling, and heat pain detection) by electromyography and quantitative sensory testing. The detection thresholds for cold and heat pain on the foot were higher in patients with, than those without MHE. This hyposensitivity was correlated with attention deficits. Reaction times in the foot were longer in patients with, than without MHE. Patients with normal sural nerve amplitude showed altered thermal sensitivity and autonomic function, with stronger alterations in patients with, than in those without MHE. MHE patients show a general decrease in cognitive and sensory abilities. Small fibers of the autonomic nervous system and thermal sensitivity are altered early on in MHE, before large sensory fibers. Quantitative sensory testing could be used as a marker of MHE.

Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study

PurposeThere are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery.Materials and MethodsThis was a prospective observational cohort study. Measurements of neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration (VPT), cold (CPT) and warm (WPT) perception thresholds, nerve conduction studies (NCS) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL); urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFRcyst-creat) and retinal grading were taken.ResultsTwenty-six (62% female; median age 52 years) obese patients with T2D were recruited. Body mass index (BMI) (47.2 to 34.5 kg/m2; p < 0.001) decreased post-operatively. There were improvements in CNFD (27.1 to 29.2/mm2; p = 0.005), CNBD (63.4 to 77.8/mm2; p = 0.008), CNFL (20.0 to 20.2/mm2; p = 0.001), NSP (3 to 0/38; p < 0.001) and eGFRcyst-creat (128 to 120 ml/min; p = 0.015) post-bariatric surgery. Changes in (Δ) triglycerides were independently associated with ΔCNFL (β = − 0.53; p = 0.024) and Δsystolic blood pressure (β = 0.62;p = 0.017), and %excess BMI loss (β = − 0.004; p = 0.018) were associated with ΔeGFRcyst-creat. There was no significant change in NDS, VPT, CPT, WPT, NCS, uACR or retinopathy status. Glomerular hyperfiltration resolved in 42% of the 12 patients with this condition pre-operatively.ConclusionBariatric surgery results in improvements in small nerve fibres and glomerular hyperfiltration in obese people with T2D, which were associated with weight loss, triglycerides and systolic blood pressure, but with no change in retinopathy or uACR at 12 months.

Quantifying the cooling effect of rain events on outdoor thermal comfort in the southern coastal stations of the Caspian Sea.

Pleasant outdoor thermal conditions depend on a wide range of climatic elements. The impact of rainfall events, as important climatic elements, on providing thermal comfort, has been less explored in the available literature. The work presented herein investigates the impact of Rainy Days as well as a Day Prior to (Dprior) and a Day Post rain (Dpost) events on thermal conditions in the southern coastal region of the Caspian Sea. In this study, rainfall events during 1961-2017 observational period were categorized based on their intensity. Then, human thermal comfort during non-rainy (sunny) and rainy days was estimated and compared by using the radiation-driven Physiological Equivalent Temperature (PET) index, Universal Thermal Climate Index (UTCI) and Perceived Temperature (PT) index. Furthermore, difference between the average of thermal conditions in rainy days compared to a day prior and a day post rain events was calculated separately for comfort, cold and heat stress thresholds of each bioclimatic index. Finally, the correlation between the average of indices for rainy days and the frequency of rainfall events of each specific year was computed. Results suggested that overall average of studied indices for all rainy days is lower than the average for days prior and post the rain events. PET index has shown to be most impacted and reduced as a result of rain events and therefore more indicative of a cool ing effect. The observed difference in total average of PET in rainy days compared to non-rainy days were 8.30°C, 5.86°C and 8.85°C for Babolsar, Rahst and Gorgan stations, respectively. Generally, the cooling effect of rain events on the temperature for a day prior rain events is higher than a day post rainfall. Finally, the trend analysis on rainy days in the studied period revealed that the average of bioclimatic indices in western stations (Babolsar and Rasht) are increasing whereas a decreasing trend was observed for Gorgan as more of an eastern station.

Associations of Small Fiber Neuropathy with Geriatric Nutritional Risk Index and Arterial Stiffness in Hemodialysis.

Background Peripheral neuropathy is a common neurological complication in uremic patients, and quantitative sensory testing (QST) is effective for diagnosis of small fiber neuropathy. Malnutrition and arterial stiffness are prevalent in patients undergoing hemodialysis (HD). The associations of small fiber neuropathy with nutritional status and arterial stiffness remain uncertain in maintenance HD patients. Methods A total of 152 HD patients were included. Geriatric nutritional risk index (GNRI), an indicator of nutritional status, was calculated by serum albumin and actual and ideal body weight. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) > 1400 cm/s. Small fiber neuropathy was assessed by an abnormal QST threshold of cold and warm sensation in patients' hands or feet. Multivariate forward logistic regression analysis was performed to examine the associations among abnormal QST threshold, GNRI, and arterial stiffness. Results baPWV and prevalence of abnormal QST threshold were significantly higher in diabetic patients. Multivariate logistic analyses revealed that older age (OR, 1.081; 95% CI, 1.026–1.139, p = 0.003) and male gender (OR, 4.450; 95% CI, 1.250–15.836, p = 0.021) were associated with abnormal warm threshold of hands. Furthermore, diabetes (OR, 3.966; 95% CI, 1.351–11.819, p = 0.012) and lower GNRI (per 1 unit increase, OR, 0.935, 95% CI, 0.887–0.985, p = 0.012) were associated with abnormal cold threshold of feet. Arterial stiffness (OR, 5.479, 95% CI, 1.132–22.870, p = 0.020) and higher calcium-phosphorus product (OR, 1.071, 95% CI, 1.013–1.132, p = 0.015) were associated with abnormal warm threshold of feet. Conclusions Lower GNRI and arterial stiffness were significantly associated with small fiber neuropathy in patients undergoing HD. Malnutrition risk and vascular factors might play important roles in small fiber neuropathy among patients undergoing HD.

Экспериментальные исследования по изучению возможности изготовления отводов холодного гнутья с увеличенными углами изгиба

Used in order to turn the line of trunk pipelines in horizontal and vertical planes, cold bends are the simplest and most economical elements to be manufactured. Their smaller rotation angle compared with other types of bends is, however, a disadvantage. The article presents the results of cold bends, experimentally manufactured from K56 strength class pipes to have an increased bending angle compared to that stated in regulatory requirements; also, it contains test results regarding metal samples taken from deformed and undeformed sites of the experimental bends. It was found that 720×8 mm and 1020×17 mm bends at rotation angles of up to 13 and 9.1°, respectively, retain satisfactory geometric parameters and are not prone to corrugations. A study on how hardening at cold deformation affects the change in the mechanical properties of deformed bend sites showed that the values of temporary resistance, yield strength, elongation, and impact strength comply with regulatory requirements. It was revealed that the delivery state of the rolled stock of the initial bare pipe affects the level of impact strength and the cold brittleness threshold attributed to the bends: thus, when testing the bent-out metal after high tempering, a higher level of toughness together with a higher cold brittleness threshold were revealed compared to those obtained when testing the bent-out metal after controlled rolling. In general, experimental studies confirmed that cold bends with an increased bending angle could be manufactured from Russian-made pipes of K56 strength class. Such bends used to construct a trunk pipeline will contribute to reducing the total number of bends, the amount of work and, consequently, the cost of construction.

Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex.

Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers. QST data of 1,252 patients (669 female, 583 male) with PNI (n=342), PNP (n=571) or CRPS (n=339), and average pain intensity reports from previously published studies were included. Absolute and z-values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects. Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (p<.05). However, after z-transformation these differences disappeared except for PPT in CRPS (p=.001). Pain thresholds in patients show only minor sex differences. However, these differences mimic those observed in healthy subjects and do not seem to be linked to specific pathophysiological processes. Female healthy participants and female patients with neuropathic pain conditions or CRPS I report lower pain thresholds compared to males, but pain intensity is similar and there is no sex difference in the extent to which the thresholds are altered in neuropathic pain or CRPS. Thus, the sex differences observed in various chronic pain conditions mimic those obtained in healthy participants, indicating that these differences are not linked to specific pathophysiological processes and are of minor clinical relevance.

Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes.

The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D). Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age-matched controls. ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm2 ) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm2 ) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm2 ) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm2 ) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED. ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non-invasive imaging method to identify small fibre damage in patients with T2D and ED.

Effects of Tonic Spinal Cord Stimulation on External Mechanical and Thermal Stimuli Perception Using Quantitative Sensory Testing: A Multicenter Stimulation ON-OFF Study on Chronic Pain Patients.

Tonic spinal cord stimulation (SCS) is currently used to treat neuropathic pain. With this type of stimulation, an implantable pulse generator generates electrical paresthesias in the affected area through 1 or more epidural leads. The goal of this study was to evaluate the impact of tonic SCS on the sensory perception of chronic pain patients using quantitative sensory testing (QST). Forty-eight patients (mean age: 57 y) with chronic leg pain due to failed back surgery syndrome or complex regional pain syndrome treated with SCS were recruited from 3 research centers. Test procedures included 2 sessions (stimulation On or Off), with measures of detection thresholds for heat, touch, vibration, and of pain thresholds for cold, heat, pressure, the assessment of dynamic mechanical allodynia, and temporal pain summation. Three different areas were examined: the most painful area of the most painful limb covered with SCS-induced paresthesias (target area), the contralateral limb, and the ipsilateral upper limb. Wilcoxon signed-rank tests were used to compare the mean difference between On and Off for each QST parameter at each area tested. P-values <0.05 were considered significant. Regarding the mean difference between On and Off, patients felt less touch sensation at the ipsilateral area (-0.4±0.9 g, P=0.0125) and were less sensitive at the contralateral area for temporal pain summation (-4.9±18.1 on Visual Analog Scale 0 to 100, P=0.0056) with SCS. It is not clear that the slight changes observed were clinically significant and induced any changes in patients' daily life. Globally, our results suggest that SCS does not have a significant effect on sensory perception.

Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants.

Chronic pain patients often suffer from insomnia or impaired sleep which has been associated with increased pain sensitivity, but a limited amount of studies have investigated the effects of total sleep deprivation on central pain mechanisms. Therefore, the aim of this study was to determine the effects of total sleep deprivation on temporal summation, conditioned pain modulation, thermal and pressure pain sensitivity in healthy participants. Twenty-four healthy participants took part in this two-session trial. The measurements were conducted after a night of habitual sleep (baseline) and following 24 hours of total sleep deprivation. Detection thresholds for cold and warmth and pain thresholds for cold and heat were assessed. Cuff induced pressure pain detection and tolerance thresholds, temporal summation and conditioned pain modulation were assessed with user-independent, computer-controlled cuff algometry. Conditioned pain modulation was significantly impaired, temporal summation was significantly facilitated and pain sensitivity to pressure and cold pain were significantly increased at follow-up compared with baseline. In conclusion, this study found that one night of total sleep deprivation impaired descending pain pathways, facilitated spinal excitability and sensitized peripheral pathways to cold and pressure pain. Future studies are encouraged to investigate if sleep therapy might normalize pain sensitivity in sleep-deprived chronic pain patients.

The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis

Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.

Observed Changes in Extreme Temperature over the Global Land Based on a Newly Developed Station Daily Dataset

AbstractThis paper presents an analysis of changes in global land extreme temperature indices (1951–2015) based on the new global land surface daily air temperature dataset recently developed by the China Meteorological Administration (CMA). The linear trends of the gridpoint time series and global land mean time series were calculated by using a Mann–Kendall method that accounts for the lag-1 autocorrelation in the time series of annual extreme temperature indices. The results, which are generally consistent with previous studies, showed that the global land average annual and seasonal mean extreme temperature indices series all experienced significant long-term changes associated with warming, with cold threshold indices (frost days, icing days, cold nights, and cold days) decreasing, warm threshold indices (summer days, tropical nights, and warm days) increasing, and all absolute indices (TXx, TXn, TNx, and TNn) also increasing, over the last 65 years. The extreme temperature indices series based on daily minimum temperatures generally had a stronger and more significant trend than those based on daily maximum temperatures. The strongest warming occurred after the mid-1970s, and a few extreme temperature indices showed no significant trend over the period from 1951 to the mid-1970s. Most parts of the global land experienced significant warming trends over the period 1951–2015 as a whole, and the largest trends appeared in mid- to high latitudes of the Eurasian continent.

Non-Gaussian Cold-Side Temperature Distribution Tails and Associated Synoptic Meteorology

Abstract Non-Gaussian cold side temperature distribution tails occur in spatially coherent patterns in winter and summer across the globe. Under such conditions, future changes in extreme cold temperature exceedances may be manifested in more complex ways than if the underlying distribution were Gaussian. For example, under a uniform warm shift, locations with shorter- or longer-than-Gaussian cold side tails would experience a more or less rapid decrease in the number of extreme cold threshold exceedances, respectively, compared to if the tail were Gaussian. In many places in the mid- to high latitudes, shorter-than-Gaussian cold tails occur where there is a climatological limit on the magnitude of cold air to be transported by synoptic flow. For example, some high-latitude regions are already among the coldest in the hemisphere, thus limiting the availability of extremely cold air, in an anomalous sense, that can be transported to the region. In other short tail regions, anomalously cold air originates from or travels over large water bodies, which limits the magnitude of the cold anomaly. Long tails are often present when the cold source region is downstream of the climatological flow, requiring a highly anomalous circulation pattern to transport the cold air. The synoptic evolution of extreme cold days at several short- and long-tailed weather stations are presented to help diagnose the mechanisms behind extreme cold temperatures under conditions of non-Gaussianity. This provides a mechanistic view of how extreme cold occurs at each location, as well as an explanation for the notable deviations from Gaussianity.

Early Biological Aging and Fetal Exposure to High and Low Ambient Temperature: A Birth Cohort Study.

Background:Although studies have provided estimates of premature mortality to either heat or cold in adult populations, and fetal exposure to ambient temperature may be associated with life expectancy, the effects of temperature on aging in early life have not yet been studied. Telomere length (TL) is a marker of biological aging, and a short TL at birth may predict lifespan and disease susceptibility later in life.Objectives:We studied to what extent prenatal ambient temperature exposure is associated with newborn TL.Methods:In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort in Flanders, Belgium, we measured cord blood and placental TL in 1,103 mother–newborn pairs (singletons with of gestation) using a quantitative real-time polymerase chain reaction (qPCR) method. We associated newborn TL with average weekly exposure to ambient temperature using distributed lag nonlinear models (DLNMs) while controlling for potential confounders. Double-threshold DLNMs were used to estimate cold and heat thresholds and the linear associations between temperature and TL below the cold threshold and above the heat threshold.Results:Prenatal temperature exposure above the heat threshold (19.5°C) was associated with shorter cord blood TL. The association with a 1°C increase in temperature was strongest at week 36 of gestation and resulted in a 3.29% [95% confidence interval (CI): , ] shorter cord blood TL. Consistently, prenatal temperature exposure below the cold threshold (5.0°C) was associated with longer cord blood TL. The association with a 1°C decrease in temperature was strongest at week 10 of gestation with 0.72% (95% CI: 0.46, 0.97) longer cord blood TL.Discussion:Our study supports potential effects of prenatal temperature exposure on longevity and disease susceptibility later in life. Future climate scenarios might jeopardize the potential molecular longevity of future generations from birth onward. https://doi.org/10.1289/EHP5153

Sophocarpine Attenuates Chronic Constriction Sciatic Nerve Injury-induced Neuropathic Pain in Mice by Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway

Background: Sophocarpine (SC) is a major alkaloid extracted from Sophora alopecuroides L. Our previous study showed that SC has analgesic effects on neuropathic pain induced by chronic constriction injury (CCI). However, the exact analgesic mechanism of SC on neuropathic pain has not yet been elucidated. Objectives: The current study aimed to examine the anti-neuropathic pain effects of SC on the HMGB1/TLR4/NF-κB signaling pathway to explore its analgesic mechanism in neuropathic pain. Methods: In this experimental study, the neuropathic pain mouse model was established by CCI of the sciatic nerve in a university-affiliated animal lab, China, 2016. Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), cold withdrawal threshold (CWT), and tail-curling latency (TCL) were used to assess the antinociceptive effect of SC in neuropathic pain mice. The mRNA and protein expression levels of HMGB1, TLR4, NF-κB, p-NF-κB, TNF-α, and IL-6 in the spinal cord of neuropathic pain mice were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results: Treatment with 40 and 20 mg/kg of SC was effective in increasing MWT, lengthening TWL, reducing CWT, and prolonging TCL in mice with neuropathic pain induced by CCI. Compared to the neuropathic-pain model group, treatment with 40 mg/kg of SC could effectively down-regulate HMGB1, TLR4, NF-κB, p-NF-κB, TNF-α, and IL-6 mRNA and protein expression levels in the spinal cord of mice with neuropathic pain induced by CCI. Conclusions: Our results showed that SC has analgesic effects on neuropathic pain induced by CCI, and its analgesic mechanism may be related to down-regulating the HMGB1/TLR4/NF-κB signaling pathway.

Local hyperalgesia, normal endogenous modulation with pain report beyond its origin: a pilot study prompting further exploration into plantar fasciopathy.

Background and aims Persistent tendinopathies were previously considered solely as peripheral conditions affecting the local tendinous tissue until quantitative sensory testing identified involvement of altered pain processing. In similar fashion, pain in patients with persistent plantar fasciopathy may also involve more than local tissue. The aim of this pilot study was to investigate potential differences in conditioned pain modulation and pressure and thermal pain thresholds, between individuals with PF and healthy pain-free controls, as a precursor to a larger-scale study. Methods We assessed 16 individuals with plantar fasciopathy and 11 pain-free controls. Plantar fasciopathy diagnosis was: palpation pain of the medial calcaneal tubercle or the proximal plantar fascia, duration ≥3 months, pain intensity ≥2/10, and ultrasound-measured plantar fascia thickness ≥4 mm. Quantitative sensory tests were performed locally at the plantar heel and remotely on the ipsilateral elbow. Assessments included pain thresholds for pressure, heat and cold, and conditioned pain modulation measured as change in local resting pressure pain threshold with cold water hand immersion. Participants rated pain intensity at pain threshold. Additionally, the area and distribution of plantar fasciopathy pain was drawn on a digital body chart of the lower limbs. Descriptive analyses were performed and between-group differences/effects expressed as standardised mean differences (d). Results There was no conditioned pain modulation difference between participants with plantar fasciopathy and controls (d = 0.1). Largest effects were on local pressure pain threshold and reported pain intensity on pressure pain threshold (d > 1.8) followed by pain intensity for heat and cold pain thresholds (d = 0.3-1.5). According to the digital body chart, pain area extended beyond the plantar heel. Conclusions The unlikelihood of a difference in conditioned pain modulation yet a pain area extending beyond the plantar heel provide a basis for exploring altered pain processing in a larger-scale study. Implications This was the first study to investigate the presence of altered pain processing in individuals with plantar fasciopathy using a conditioned pain modulation paradigm and thermal pain thresholds. We found no indication of an altered pain processing based on these measures, however, patients rated pain higher on thresholds compared to controls which may be important to clinical practice and warrants further exploration in the future.

Associations between pain thresholds for heat, cold and pressure, and Pain Sensitivity Questionnaire scores in healthy women and in women with persistent pelvic pain.

The Pain Sensitivity Questionnaire (PSQ) is a self-rating instrument developed as a time- and cost-saving alternative to quantitative sensory testing (QST). The aims of the study were to assess (a) the associations between PSQ scores and QST in women with persistent pelvic pain and in pain-free controls and (b) to what extent demographic variables and psychological distress influenced PSQ scores. Fifty-five healthy women and 37 women with persistent pelvic pain participated. All filled in the PSQ and Hospital Anxiety and Depression Scale and had QST (heat, cold and pressure pain thresholds) performed on six locations on the body. Information on age, body mass index, smoking habits and pain duration were collected. Principal component analysis and orthogonal partial least square regressions were used. The patients scored significantly higher on PSQ than the controls. Significant multivariate correlations between pain thresholds and PSQ scores were found only in the patient group. In the patient group, the heat and cold pain thresholds correlated more strongly with PSQ scores than the pressure pain threshold. The PSQ score was significantly higher in pelvic pain patients, and correlations between QSTs and the PSQ were only found for patients. The PSQ reflects pain sensitivity in women with PPP and can be used as a non-invasive and painless way to assess this condition in clinical practice.