Warm Detection Research Articles

Effect of Topical Analgesia on Desensitization Following 8% Topical Capsaicin Application

To prevent pain associated with 8% capsaicin application, pretreatment with local anesthetics, such as EMLA (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), is considered an option. However, there is contradicting evidence regarding the effects of local analgesia on capsaicin-induced desensitization. In session 1, 2 skin areas in each forearm of 24 healthy volunteers were randomized to 2-hour pretreatment with EMLA/placebo cream. After pretreatment, 8% capsaicin patches were applied for 3 hours in 1 placebo and 1 EMLA pretreated area, obtaining the following four areas: Capsaicin + EMLA, Capsaicin + Placebo, EMLA alone, and Placebo. Pain intensity scores were assessed during the 3-hour application of capsaicin. Warmth detection, heat pain sensitivity, and microvascular reactivity were measured after the removal of capsaicin. After 24 hours, in session 2, all tests were repeated followed by histamine application in each area to examine itch intensity and neurogenic flare.Overall, EMLA caused significant reductions in capsaicin-induced pain compared with placebo (P= .007) and enhanced the capsaicin-induced increase in superficial blood perfusion immediately after the 3-hour capsaicin application (P< .01). Regardless of pretreatment, capsaicin induced heat hyperalgesia immediately after the application (P< .001). Twenty-four hours post application, heat pain sensitivity was normalized. However, WDT increased significantly (P< .001). Capsaicin tended to reduce the itch intensity and significantly reduced the neurogenic flare (P< .05) induced by histamine compared with EMLA alone. The findings suggest that pretreatment with topical analgesic cream reduces application site pain without interfering with the 8% topical capsaicin-induced desensitization. PerspectivePretreatment with local anesthetic EMLA cream might be considered a good therapeutic option to reduce the pain associated with 8% capsaicin application currently used for treatment of neuropathic pain syndromes. This study also suggests the existence of a synergistic effect of capsaicin and EMLA on the process of neurogenic inflammation.

Can within-subject comparisons of thermal thresholds be used for diagnostic purposes?

ObjectiveQuantitative thermal testing (QTT) is a psychophysical assessment method of small nerve fibers that relies on reference material to assess function. Normal limits for within-subject comparisons of thermal thresholds are scarce, and their association with age, height and sex is not fully elucidated. The aim of this study was to investigate the normal limits for distal-proximal– and contralateral homologous comparisons of thermal thresholds with QTT, and their association with age, sex or height. MethodsFifty healthy volunteers ages 20–79 participated in the experiment. Cold detection thresholds (CDT), warm detection thresholds (WDT), heat pain thresholds (HPT), and cold pain thresholds (CPT) were measured bilaterally at the thenar eminence, anterior thigh, distal medial leg and foot dorsum. Sample normal limits were calculated as (mean) ± 2 SD. ResultsForty-eight subjects were included in the analysis. CPT was excluded from all analyses due to a large floor-effect. Sample normal limits for side-differences ranged from 1.8 to 7.2 °C for CDT, 2.4–6.8 °C for WDT and 3.2–4.0 °C for HPT, depending on anatomical site. For distal-proximal comparisons, sample normal limits ranged from 4.0 to 8.7 °C for CDT, 6.0–14.0 °C for WDT and 4.2–9.0 °C for HPT, depending on the pairs compared. Age was associated with side-differences for CDT in the thenar eminences (p < 0.001) and distal medial legs (p < 0.002), and with 11 of 18 distal-proximal comparisons (p < 0.01). ConclusionsThe normal limits for distal-proximal- and contralateral homologous thermal thresholds were wide, and thus of limited use in a clinical setting, although the reported values may be somewhat inflated by low sample-size and consequent age-pooling. Age, but not sex or height, was associated with contralateral differences in CDT in the thenar eminences and distal medial legs, and with most distal-proximal differences. SignificanceDue to wide normal limits, we advise caution when utilizing relative comparisons of thermal thresholds for diagnostic purposes.

Pain sensitivity in young adults with juvenile idiopathic arthritis: a quantitative sensory testing study

BackgroundTo study for the first-time, pain perception, pain sensitivity, and self-reported pain in young adults with long disease duration of juvenile idiopathic arthritis (JIA) compared with controls.MethodsChildren from Central Norway diagnosed with JIA between 1997 and 2004 were included consecutively in a population-based prospective study. Children with onset 1997–2000 were part of the Nordic JIA cohort. Controls were age- and sex-matched. In 2015–2017, study visits with investigator-blinded quantitative sensory testing (QST) comprising cold and warm detection thresholds (CDT/WDT), cold and heat pain thresholds (CPT/HPT), pressure pain threshold (PPT), and a suprathreshold heat pain test were performed. We constructed separate multilevel models for each variable of detection and pain thresholds with interaction between groups and site adjusted for the effect of age and sex.ResultsAmong 96 young adults with JIA, 71% were female, median age was 22.7 years, disease duration was 16.1 years, and 47% had oligoarticular disease. Among 109 controls, 71% were female, and median age was 23.5 years. Participants with JIA had lower pressure pain thresholds (PPTs) (95% CI) compared to controls, upper limb 888 (846,930) versus 1029 (999,1059) kPa and lower limb 702 (670,734) versus 760 (726,794) kPa. Participants with inactive disease had the lowest PPTs and cold pain thresholds (CPTs), compared to those in remission off medication and those with active disease. Minor differences were found regarding CDT/WDT and CPT/HPT in JIA compared to controls. The median (IQR) temperature needed to evoke pain = 6 on a 0–10 numeric rating scale (NRS) in the suprathreshold heat pain tests were lower in JIA than in controls (46 °C (45–47 °C) versus 47 °C (46–48 °C)). We found no associations between self-reported pain and pain thresholds.ConclusionsOur results indicate for the first time that young adults with long disease duration of JIA may have altered pain perception and sensitivity compared to controls. A clinical implication may be the importance of early treatment to quickly achieve pain-free remission and avoid long-term pain sensitization.

Measures of central sensitization and their measurement properties in musculoskeletal trauma: A systematic review.

Chronic pain following musculoskeletal trauma is common, which may partially be attributed to the early presence of central sensitization (CS). Multiple measures are suggested to assess clinical features of CS, yet no systematic review has evaluated the measurement properties of these measures in a musculoskeletal trauma population. This systematic review, which followed a published and PROSPERO registered protocol (CRD42018091531), aimed to establish the scope of CS measures used within a musculoskeletal trauma population and evaluate their measurement properties. Searches were conducted in two stages by two independent reviewers. The Consensus-based Standards for the selection of Health Measurement Instruments (COSMIN) checklist was used to evaluate risk of bias and overall quality was assessed using the modified Grading of Recommendations Assessment, Development and Evaluation. From 86 studies, 30 different CS outcome measures were identified. Nine studies evaluated measurement properties of nine outcome measures; eight evaluated reliability and one evaluated construct validity. Measures included seven quantitative sensory testing methods (pressure, cold and electrical pain thresholds; warm, cold and vibration detection thresholds; vibration perception thresholds), pain drawings and a pinwheel. Risk of bias was assessed as doubtful/inadequate for all but one study, overall quality of evidence was low/very low for all measures. Reliability of measures ranged from poor to excellent. Many measures are used to evaluate CS but with limited established measurement properties in musculoskeletal trauma. High quality research to establish measurement properties of CS outcome measures is required.

Quantitative sensory phenotyping in chronic neuropathic pain patients treated with unilateral L4-dorsal root ganglion stimulation

BackgroundIn a previous study, we reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRGSTIM-related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRGSTIM effects in CRPS patients.MethodsTwelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRGSTIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area.ResultsAt baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRGSTIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRGSTIM.ConclusionsSelective L4-DRGSTIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics.The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267).https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267

Thermal sensitivity mapping - warmth and cold detection thresholds of the human torso.

Skin as the largest organ of the human body accomplishes many important functions, including thermoregulation. In this context, investigating cold (CDT) and warmth detection thresholds (WDT) constitutes an important research branch, and investigating thermal thresholds has a significant impact on the clothing and fabric textile industry. In this regard, not only the extremities, but also torso regions are of high relevance. However, only few examinations have conducted detailed mapping studies of the human torso. Additionally, some of these studies show certain methodological limitations. Furthermore, the issue of whether cutaneous thermal sensitivity is gender-dependent is still controversial. Therefore, the present study investigated the cutaneous thermal sensitivity (CDT, WDT) of 42 male and female young and healthy subjects. Measurements were taken at 11 anatomical regions. We found that gender plays an important role when investigating thermal thresholds: Females tended to be more sensitive than males. We also found considerable differences between the tested regions, even within the anterior torso, for example. We identified locations which were constantly sensitive (lower back), while others were consistently insensitive (e.g. scapula). We also detected greater data variability for males compared to females, and for WDT compared to CDT. Furthermore, mainly for WDT, we found a proximal-to-distal increase of thermal torso and upper arm sensitivity. In line with previous investigations, our subjects were more sensitive to cold than to warmth. The findings of this study have important implications. First, our data may complement basic research, e.g. in terms of reference data of body regional maps. Second, our data provides important insights that could be leveraged in the textile industry, and also used to optimize current broadly applicable test methods and tools, like thermal manikins and thermophysiological models.

Sweet taste does not modulate pain perception in adult humans.

Background: Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

Assessing thermal sensitivity using transient heat and cold stimuli combined with a Bayesian adaptive method in a clinical setting: A proof of concept study.

Quantitative sensory testing of thermal detection abilities is used as a clinical tool to assess the function of pain pathways. The most common procedure to assess thermal sensitivity, the 'method of limits', provides a quick but rough estimate of detection thresholds. Here, we investigate the potential of evaluating not only the threshold but also the slope of the psychometric functions for cold and warm detection. A convenience sample of 15 patients with diabetes mellitus (DM) and 15 age-matched healthy controls (HC) was tested. Thirty brief (100ms) stimuli of each modality were applied to the volar wrist and foot dorsum. Cold and warm stimuli were delivered with a Peltier thermode and a temperature-controlled CO2 laser, respectively. Stimulus intensities were dynamically selected using an adaptive Bayesian algorithm (psi method) maximizing information gain for threshold and slope estimation. ROC analyses were used to assess the ability of slopes, thresholds and the combination of both to discriminate between groups. Assessment of the slope and threshold of the psychometric function for thermal detection took about 10min. The ability to detect warmth was not reduced in DM patients as compared to HC. Cold detection performance assessed using slope or threshold parameters separated DM from HC with good discriminative power. Discrimination was further increased when both parameters were used together (93% sensitivity and 87% specificity), indicating that they provide complementary information on patient status. The psi method may be an interesting alternative to the classical method of limits for thermal QST. Current QST protocols provide an incomplete and potentially biased estimate of sensory detection performance. We propose a method that estimates the slope and the threshold of the psychometric function, defining heat and cold sensory detection performance, in only a few minutes. Furthermore, we provide preliminary evidence that combining slope and threshold parameters of cold detection performance leads to a better discriminative ability than relying solely on the threshold.

Adjunctive effects of laser therapy on somatosensory function and vasomotor regulation of periodontal tissues in patients with periodontitis: A randomized controlled clinical trial.

The purpose of this prospective study was to compare the changes in periodontal somatosensory function and microcirculation in patients with periodontitis following initial treatment with scaling and root planing (SRP) with or without adjuvant laser therapy. Twenty-four patients suffering from periodontitis were recruited and randomly allocated into a split-mouth design to either SRP combined laser therapy side (test side) or SRP only side (control side). All treatments were performed by the same investigator at a single visit. Laser Doppler Flowmetry (LDF) and Quantitative Sensory Testing (QST) were performed at baseline (W0), 1week (1W), 2weeks (2W), and 4weeks (4W) after treatment on both sides of the attached gingiva of the maxillary lateral incisor. Clinical examination including probing depth (PD) and bleeding on probing (BOP) was performed at W0, 2W, and 4W on both sides. Data were analyzed with two-way analysis of variance. PD and BOP significantly improved after treatment (P<0.001). LDF values were significantly decreased on both sides at all follow-up time points (P<0.001), temperature was increased only on the test side (P=0.017) whereas there was no significant change on the control side (P=0.792). Significantly less sensitivity was observed for all QST parameters (P<0.030) except for warmth detection after treatment. Adjunctive use of laser therapy did not provide any significant clinical advantage or additional effects on the recovery of periodontal somatosensory function or gingival microcirculation in the present study.

Sweet taste does not modulate pain perception in adult humans

Background: Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

Psychophysical characterisation of burning mouth syndrome-A systematic review and meta-analysis.

Primary burning mouth syndrome (BMS) is an oro-facial disease with neuropathic characteristics. Psychophysics, such as quantitative sensory testing (QST), is used to sub-classify neuropathic pain syndromes, but their usefulness in characterising BMS is not yet clear. The aim of this study was to summarise and to quantitatively and qualitatively analyse the available information about QST findings in BMS, and to reflect on possible mechanisms of disease. In this systematic review and meta-analysis, different search strategies were used to screen for articles in PubMed, Embase, EBSCOhost, Cochrane Library, Web of Science, Google Scholar and two sources of conference abstracts. Primary clinical studies focused on QST assessment in patients with BMS were included. Data were synthesised qualitatively and quantitatively. Risk of bias was assessed following the AHRQ guidelines. Thirteen articles with low to moderate risk of bias and one conference abstract were selected from 45 unique articles that were identified. Individually, the studies reported combinations of thermal and mechanical sensory impairments measured by QST. The meta-analysis showed significant sensory differences between patients and controls in warmth (effect size=0.683; P<.05) and cold detection thresholds (effect size=-0.580; P<.001). The results indicate that thermal sensitivity seems to be altered in patients with BMS compared to controls, suggesting a small-fibre neuropathy. However, study protocols were highly variable and heterogeneous. Therefore, studies with better designs and complete reporting of results should be performed to bring value to the use of psychophysics in the assessment of BMS.

Effect of Directional Deep Brain Stimulation on Sensory Thresholds in Parkinson's Disease.

ObjectivePrevious studies showed that deep brain stimulation (DBS) relieves pain symptoms in Parkinson disease (PD) patients when programmed for motor-symptom relief. One factor involved in pain processing is sensory perception of stimuli. With the advent of directional leads, we explore whether directional DBS affects quantitative sensory testing (QST) metrics acutely.MethodsPD patients with subthalamic (STN) DBS and directional leads were tested in 5 settings (DBS-OFF, DBS-ON with omnidirectional stimulation, and DBS-ON) for each of three directional segments of contact used for clinical programming. The Unified Parkinson’s Disease Rating Scale (UPDRS-III) assessed patient’s motor skills at time of study visit at clinical contact and at contact which produced optimal sensory threshold (defined by the greatest tolerance to mechanical stimuli). Correlation analyses were performed between stimulation parameters [amplitude, frequency, pulse width (PW), total electrical energy delivered (TEED)] and outcome metrics.ResultsSensory thresholds were obtained in nine patients. Directional stimulation did not significantly alter patient perceptions of sensory stimulus [cold pain (p = 0.69), warm pain (p = 0.99), Von frey fibers (p = 0.09), pin-prick (p = 0.88), vibration (p = 0.40), pressure (p = 0.98)]. With correlation analysis, increasing PW at the posterior contact increased pin prick and vibration sensitivity (p < 0.001). Additionally, an increase in TEED caused a decrease in sensitivity to warm detection when using the anterior (p = 0.04), lateral (p = 0.02), and medial contacts (p = 0.03), and also caused a decrease in sensitivity to cold detection when using the medial contact (p = 0.03). UPDRS-III remained stable during testing.ConclusionMotor benefit can be acutely maintained at directional contacts, whereas directional stimulation can modulate thermal and mechanical sensitivity. Further investigation will determine whether these changes are maintained chronically or can be improved with optimized programming.

Abstract D044: Age and sex effects on quantitative sensory testing values in healthy African American adults

Abstract Introduction: Only a few studies have reported quantitative sensory testing (QST) reference values for healthy African Americans, and those studies are limited in sample size and range of age of participants. The intent of our study was to fill a gap in the understanding of pain and somatosensory function in African Americans by generating QST values for healthy African American adults. In a large cohort of pain-free, healthy African American adults whose past pain experiences and current psychological status were known, our study aim was to determine thermal and mechanical QST values and compare those values at the anterior forearm by age and sex. We also determined the values for 5 other body sites and compared the values for differences by testing site location (upper body versus lower body). Methodology: In this cross-sectional study, 124 pain-free African American adults (age 18 to 69 years, 49% female) completed demographic and self-reported pain, fatigue and psychosocial measures. QST included obtaining thermal and mechanical responses and associated pain intensity levels. We applied the Benjamini-Hochberg procedure to adjust the p values to account for the multiple t tests. Results: We found thermal detection values at the anterior forearm were (29.2°C±1.6) for cool detection (CD) and (34.5°C±1.2) for warm detection (WD). At that site, pain thresholds were: cold pain threshold (CPTh) (26.3°C±5.0), heat pain threshold (HPTh) (37.8°C±3.6), and mechanical pain thresholds (MPTH) (16.7±22.2 grams of force, gF). There was a significant between sex difference for WD, with women being more sensitive (q=0.027). Lower body sites were less sensitive than upper body sites across all thermal modalities (q&amp;lt;0.003), but not for the mechanical modality. Mean pain intensity scores rated immediately after the CPTh and HPTh were 1.9 ± 1.3 to 2.2 ± 1.2 on the 0-10 pain intensity scale. Similarly, after the MPTh tests the mean pain intensity scores were 0.5 ± 0.5 to 0.8 ± 0.6. These scores did not differ significantly by sex or age group and clearly indicate that the participants reported pain threshold at an appropriately low perceptual intensity. Pain intensity values for past pain experiences and low ratings for fatigue, depression and anxiety indicated that these factors were unlikely contributors to their pain threshold reports. Conclusion: The QST values from this protocol at the anterior forearm indicate that healthy African American adults had average thermal pain thresholds within 6°C of the temperature of adaptation and average MPTh under 20 gF. Differences in responses to thermal and mechanical stimuli for upper verses lower body were consistent with prior research. These findings add to the body of literature confirming that African American adults indeed have lower pain thresholds than those reported for White adults. These QST values can be used as controls for African Americans with cancer to understand the neuropathic pain syndromes associated with tumor progression and cancer treatments. Citation Format: Keesha L. Powell-Roach, Starja Q. Booker, Yingwei Yao, Marie L. Suarez, Miriam O. Ezenwa, Roger B. Fillingim, Zaijie J. Wang, Robert E. Molokie, Diana J. Wilkie. Age and sex effects on quantitative sensory testing values in healthy African American adults [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D044.

Detecting Warm Temperatures Is a Cool Kind of Thing

In this issue of Neuron, Paricio-Montesinos etal. (2020) unveil the essential cellular elements for warm temperature detection in mice. Surprisingly, the silencing of spontaneously firing, unmyelinated, polymodal sensory afferents harboring cold-activated TRPM8 channels is the key neural mechanism.

Sweet taste does not modulate pain perception in adult humans.

Background: It is commonly observed that humans who are in pain or discomfort seek solace in the form of sweet foods and drinks. Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

Comparison of Three Availability Systems with Warm Standby Components, Detection Delay, and General Repair Times

This study analyzes three availability systems with warm standby units, fault detection delay, and general repair times. The failure times and repair times of failed components were assumed to follow exponential and general distributions, respectively. The detection delay times were assumed to be exponentially distributed. This study exploited the supplementary variable technique to develop a recursive method for deriving the steady-state availability for three systems. By using extensive numerical computations, we compared three systems in terms of system availability based on specific values given to the system parameters. The state transition rate diagrams of the three systems revealed the symmetry property approximately. The three systems were ranked based on the system availability and the cost/benefit for the three various repair time distributions: exponential, three-stage Erlang, and deterministic, where the benefit was system availability.

Quantitative sensory testing of periauricular skin in healthy adults

The aim of this study was to investigate the test-retest reliability of quantitative sensory testing (QST) and mechanical sensitivity mapping of the periauricular skin. Twenty volunteers (10 men, 10 women) participated in two sessions at intervals of one week. Cold and warm detection threshold (CDT&WDT), cold and heat pain threshold (CPT&HPT), mechanical detection and pain threshold (MDT&MPT), pressure pain threshold (PPT) and two-point discrimination (2PD) were measured at five sites: bilateral subauricular and postauricular sites (LA, RA, LB, RB) and the dorsum of left hand (control). Pressure stimulation was applied at each of the four periauricular test sites. The test-retest reliability of the QST data implied fair to excellent agreement as evaluated by the intra-class correlation coefficients (ICC; all >0.4) for different days. There was no difference between each side in the QST parameters and mechanical sensitivity mapping (P ≥ 0.057). Significant differences between subauricular and postauricular sites were shown for WDT and PPT (P ≤ 0.028). NRS scores of mechanical sensitivity mapping showed significant effects of gender, site and point (P ≤ 0.040). QST and mechanical sensitivity mapping can be considered to be a reliable technique to assess somatosensory function of the periauricular skin.

Thermal Psychophysics and Associated Brain Activation Patterns Along a Continuum of Healthy Aging.

ObjectiveTo examine psychophysical and brain activation patterns to innocuous and painful thermal stimulation along a continuum of healthy older adults.DesignSingle center, cross-sectional, within-subjects design.MethodsThermal perceptual psychophysics (warmth, mild, and moderate pain) were tested in 37 healthy older adults (65–97 years, median = 73 years). Percept thresholds (oC) and unpleasantness ratings (0–20 scale) were obtained and then applied during functional magnetic resonance imaging scanning. General linear modeling assessed effects of age on psychophysical results. Multiple linear regressions were used to test the main and interaction effects of brain activation against age and psychophysical reports. Specifically, differential age effects were examined by comparing percent-signal change slopes between those above/below age 73 (a median split).ResultsAdvancing age was associated with greater thresholds for thermal perception (z = 2.09, P = 0.037), which was driven by age and warmth detection correlation (r = 0.33, P = 0.048). Greater warmth detection thresholds were associated with reduced hippocampal activation in “older” vs “younger” individuals (>/<73 years; beta < 0.40, P < 0.01). Advancing age, in general, was correlated with greater activation of the middle cingulate gyrus (beta > 0.44, P < 0.01) during mild pain. Differential age effects were found for prefrontal activation during moderate pain. In “older” individuals, higher moderate pain thresholds and greater degrees of moderate pain unpleasantness correlated with lesser prefrontal activation (anterolateral prefrontal cortex and middle–frontal operculum; beta < –0.39, P < 0.009); the opposite pattern was found in “younger” individuals.ConclusionsAdvancing age may lead to altered thermal sensation and (in some circumstances) altered pain perception secondary to age-related changes in attention/novelty detection and cognitive functions.

Quantitative sensory testing predicts histological small fiber neuropathy in postural tachycardia syndrome.

Retrospective investigation of the somatosensory profile and prediction of histologic small fiber neuropathy (SFN) in postural orthostatic tachycardia syndrome (POTS) was performed using quantitative sensory testing (QST) as a standardized noninvasive test. In this investigation, full data sets from 30 patients (age: 34.03 ± 10.82 years, n = 6 males), including results of autonomic function testing, norepinephrine values, skin biopsy, and QST, were retrospectively analyzed. The QST data were compared with healthy controls (HCs) (age: 34.20 ± 10.5 years, n = 6 males, t test: 0.95). The evaluation of all QST parameters in POTS compared with HCs yielded differences in all thermal parameters (cold detection threshold: p < 0.05, warm detection threshold: p < 0.001, thermal sensory limen: p < 0.001, cold pain threshold: p < 0.05, and heat pain threshold: p < 0.001) and in paradoxical heat sensations (p < 0.05). Differences in nonpainful stimuli (mechanical detection threshold: p < 0.05 and vibration detection threshold: p < 0.001) were also detected. All patients who had clinical signs of SFN in combination with impairment of small fibers in QST also had SFN on skin biopsy. These results suggest that a non-region-specific SFN in POTS compared with controls can be detected by noninvasive QST that predicts histologic small fiber pathology.

Effect of intravenous dexamethasone on the anaesthetic characteristics of peripheral nerve block: a double-blind, randomised controlled, dose–response volunteer study

BackgroundIntravenous dexamethasone is thought to prolong the duration of peripheral nerve block, but the dose–response relationship remains unclear. The aim of this volunteer study was to evaluate the dose–response effect of i.v. dexamethasone on the prolongation of median nerve block. MethodsIn a double-blind, randomised controlled study, 18 volunteer subjects received two median nerve blocks separated by a washout period. One block was conducted alongside an infusion of saline and the other alongside i.v. dexamethasone 2, 4, or 8 mg. The primary outcome was time to return of normal pinprick sensation. Secondary outcomes included thermal quantitative sensory testing (QST) for the time to return of cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), area under QST curves, grip strength, and the incidence of adverse effects. ResultsThe primary outcome, time to recovery of pinprick sensation, was similar between volunteers receiving saline or i.v. dexamethasone, regardless of dose (P=0.99). The time to recovery of QST milestones was similar between groups, although area under QST curves indicated prolongation of CDT (0 vs 8 mg, P=0.002) and WDT (0 vs 2 mg, P=0.008; 0 vs 4 mg, P=0.001; 0 vs 8 mg, P<0.001). There was no difference in motor recovery or adverse effects. ConclusionsIntravenous dexamethasone failed to significantly prolong the duration of pinprick anaesthesia regardless of dose. However, area under QST curve analysis indicated a dose-independent prolongation of CDT and WDT, the clinical significance of which is unclear. Clinical trial registrationNCT02864602 (clinicaltrials.gov).