Cold Perception Thresholds Research Articles

Genetic Factors Associated with the Development of Neuropathy in Type 2 Diabetes.

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index. Sensory nerve function was estimated by Neurometer and Medoc devices. Neuropathic symptoms were characterized by the neuropathy total symptom score (NTSS). Whole exome sequencing (WES) was performed on a Thermo Ion GeneStudio S5 system determining the coding sequences of approximately 32,000 genes comprising 50 million base pairs. Variants were detected by Ion Reporter software and annotated using ANNOVAR, integrating database information from dbSNP, ClinVar, gnomAD, and OMIM. Integrative genomics viewer (IGV) was used for visualization of the mapped reads. We have identified genetic variants that were significantly associated with increased (22-49-fold) risk of neuropathy (rs2032930 and rs2032931 of recQ-mediated genome instability protein 2 (RMI2) gene), rs604349 of myosin binding protein H like (MYBPHL) gene and with reduced (0.07-0.08-fold) risk (rs917778 of multivesicular body subunit 12B (MVB12B) and rs2234753 of retinoic acid X receptor alpha (RXRA) genes). The rs2032930 showed a significant correlation with current perception thresholds measured at 5 Hz and 250 Hz for n. medianus (p = 0.042 and p = 0.003, respectively) and at 5 Hz for n. peroneus (p = 0.037), as well as the deep breath test (p = 0.022) and the NTSS (p = 0.023). The rs2032931 was associated with current perception thresholds (p = 0.003 and p = 0.037, respectively), deep breath test (p = 0.022), and NTSS (p = 0.023). The rs604349 correlated with values measured at 2000 (p = 0.049), 250 (p = 0.018), and 5 Hz (p = 0.005) for n. medianus, as well as warm perception threshold measured by Medoc device (p = 0.042). The rs2234753 showed correlations with a current perception threshold measured at 2000 Hz for n. medianus (p = 0.020), deep breath test (p = 0.040), and NTSS (p = 0.003). There was a significant relationship between rs91778 and cold perception threshold (p = 0.013). In our study, genetic variants have been identified that may have an impact on the risk of neuropathy developing in type 2 diabetic patients. These results could open up new opportunities for early preventive measures and might provide targets for new drug developments in the future.

Quantitative sensory testing defines the trajectory of sensory neuropathy after severe COVID-19

AimsTo assess sensory neuropathy development after severe COVID-19. MethodsPatients with severe COVID-19 underwent assessment of neuropathic symptoms, tendon reflexes, and quantitative sensory testing to evaluate vibration (VPT), cold (CPT), warm (WPT) and heat perception thresholds (HPT) within 1–3 weeks of admission and after 1-year. Results32 participants with severe COVID-19 aged 68.6 ± 12.4 (18.8 % diabetes) were assessed. At baseline, numbness and neuropathic pain were present in 56.3 % and 43.8 % of participants, respectively. On the feet, VPT, WPT, and HPT were abnormal in 81.3 %, CPT was abnormal in 50.0 % and HPT on the face was abnormal in 12.5 % of patients. At 1-year follow-up, the prevalence of abnormal VPT (81.3 % vs 50.0 %, P < 0.01), WPT (81.3 % vs 43.8 %, P < 0.01), and HPT (81.3 % vs 50.0 %, P < 0.01) decreased, with no change in CPT (P = 0.21) on the feet or HPT on the face (P = 1.0). Only participants without diabetes recovered from an abnormal VPT, CPT, and WPT. Patients with long-COVID (37.5 %) had comparable baseline VPT, WPT and CPT with those without long-COVID (P = 0.07–0.69). ConclusionsSevere COVID-19 is associated with abnormal vibration and thermal thresholds which are sustained for up to 1 year in patients with diabetes. Abnormal sensory thresholds have no association with long-COVID development.

The role of chemokines in type 1 diabetes-associated neuropathy.

To investigate whether circulating chemokines contribute to the development of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes (T1D). Fifty-two patients with childhood-onset T1D (mean age 28 ± 4 yrs.; diabetes duration 19.5 ± 5.5 yrs.) and 19 control subjects (mean age 26.5 ± 4.5 yrs.) were included in a cross-sectional analysis of this long-term longitudinal cohort study. A subgroup of 24 patients was followed prospectively for a further 10 yrs. Plasma levels of Th1- (CXCL9, CXCL10 and CXCL11), Th2- (CCL17 and CCL22) and Th17-associated (CXCL8 and CCL20) chemokines were assessed in all subjects. Additionally, the TID patients underwent clinical examination and electroneurography. The frequency of neuropathy was 21% (11/52). Higher levels of CXCL9 levels were found in patients with DPN compared with control subjects (p = .019); by contrast, no difference between patients without DPN and control subjects was seen after adjustment for multiple comparisons. In patients with DPN, CXCL10 correlated negatively with suralis MCV and suralis SNAP (rho -0.966, p < .001 and rho -0.738, p < .001, respectively) and was positively correlated with the vibration perception threshold (rho 0.639, p = .034), while CXCL8 correlated negatively with the cold perception threshold (rho -0.645, p = .032). The frequency of neuropathy increased to 54% (13/24) in the subgroup of 23 TID patients, followed by an additional 10 yrs. Changes in Th1- and Th17-associated chemokines were associated with impaired peripheral sensory nerve function and nerve conduction after long disease duration in childhood-onset T1D.

459-P: Effects of Liraglutide on Somatic Nerve Function in Subjects with Type 2 Diabetes

Background: Preclinical data has shown that GLP-1 receptor agonists play a role in nerve regeneration and repair. However, few studies have investigated the effects of these compounds on nerve function in humans. The aim of this study was to examine the effect of Liraglutide (Lira) on somatic nerve function in patients with type 2 diabetes. Methods: Randomized, double-blind, placebo-controlled study of Lira 1.8 mg daily for 52 weeks. All participants were evaluated with the following somatic nerve function tests: Utah Early Neuropathy Scale (UENS) , quantitative sensory testing (QST) for cold and warm perception thresholds (Q-Sense v6.0.13.1; Medoc - Minneapolis, MN) , nerve conduction studies (NCS) (Sierra Summit System; Cadwell Industries - Kennewick, WA) and in vivo corneal confocal microscopy (CCM) to measure corneal nerve fiber density, branching and length (Tomograph III; Heidelberg Engineering - Smithfield, Rhode Island) Results: We randomized 44 subjects (21 to Lira and 23 to pb) . Baseline characteristics were similar. Main results are shown in Table 1. In both groups, there was no significant change on UENS, QSTs, NCS and CCM measures after 1 year of treatment. The results also were not significantly different between the groups. Conclusions: This study did not show improvements in somatic nerve function after 52 weeks of treatment with Lira. The small sample size may have contributed to the negative result. Disclosure C.M.Casellini: Advisory Panel; Nevro Corp. H.Parson: None. M.D.Bailey: None. E.S.Siraj: Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk. Funding Novo Nordisk (Grant#15-12-FB-0218)

NEURO TOUCH: A novel digital device for assessment and screening of peripheral neuropathy

BackgroundMost of the patients suffering from diabetes develop Sensory neuropathy which proceeds with development of painful neuropathy. This can lead to formation of ulcers in later stages. Currently, available Quantitative Sensory Testing (QST) devices take more time to perform and are expensive. NEURO TOUCH is such device which combines four parameters of QST in one unit. Its portable, battery operated and handy device with real time display of results along with data storage and data transfer facility. It can perform tactile sensation threshold, vibration and thermal testing threshold along with skin temperature measurement. This study was undertaken to establish the diagnostic validity, reproducibility and repeatability for early detection of peripheral neuropathy. MethodsA total of 317 subjects were recruited for QST assessment with NEURO TOUCH; Tactile threshold sensation, vibration perception and thermal threshold testing along with skin temperature. A subset of 30 subjects in each group were considered for repeatability and reproducibility test. ResultsThe mean difference for vibration perception threshold was 0.6 when compared with gold standard device. Regarding the cold and warm perception threshold the mean difference was 1.1 and 2 °C respectively when compared with gold standard device. For skin temperature measures there was a mean difference of 1.2 °C with respect to standard device. ConclusionsThe NEURO TOUCH device was easy-to-use, compact and provided an efficient multimodality approach which can help for screening of peripheral neuropathy patients with type 2 diabetes.

Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.

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.

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.

021 The Role of Office-Based Somatic and Autonomic Neuro-Genital Testing of Persistent Genitourinary Numbness in Women

In women with sexual dysfunction, a bothersome/distressing symptom is persistent numbness in the genitourinary region, the clitoris, vagina and urethra. Women with persistent numbness often find it difficult to feel their clitoris when touched, or feel objects placed within their vagina, or feel urine flowing in their urethra. This symptom often leads to orgasmic dysfunction and limited sexual pleasure. Using office-based neuro-genital testing, we examined the integrity of the somatic and autonomic neurologic pathways of genitourinary sensation to better understand the etiology of female genitourinary sensory impairment. Office-based neuro-genital testing includes quantitative sensory testing, sacral and foot dermatome testing, bulbocavernosus reflex latency testing, vaginal pelvic afferent nerve testing and urethral pelvic afferent nerve testing. Quantitative sensory testing measures somatic vibration, cold, and heat perception threshold values in the glans clitoris, right and left inner surface of labia minora, and uses the right pulp index finger threshold values as the control. Sacral and foot dermatome testing measures somatic vibration perception in the right and left gluteal, thigh, calf, heel, arch, medial and lateral aspects of the foot, using the right pulp index finger threshold values as the control. Bulbocavernosus reflex latency testing with electromyographic monitoring of the external anal sphincter muscle contraction measures the integrity of the somatic sensory and motor neural pathways in response to mechanical stimulations of the glans clitoris. The vaginal pelvic afferent neural pathway test measure visceral awareness of distension of an anorectal (up to 60 ml) balloon within the vagina. The urethral pelvic afferent neural pathway test measure visceral awareness of distension of a Foley catheter (up to 0.4 ml) balloon within the urethra.

Long-term effect of hand-arm vibration on thermotactile perception thresholds

BackgroundOccupational exposure to hand-transmitted vibration (HTV) is known to cause neurological symptoms such as numbness, reduced manual dexterity, grip strength and sensory perception. The purpose of this longitudinal study was to compare thermotactile perception thresholds for cold (TPTC) and warmth (TPTW) among vibration exposed manual workers and unexposed white collar workers during a follow-up period of 16 years to elucidate if long-term vibration exposure is related to a change in TPT over time.MethodsThe study group consisted of male workers at a production workshop at which some of them were exposed to HTV. They were investigated in 1992 and followed-up in 2008. All participants were physically examined and performed TPT bilaterally at the middle and distal phalanges of the second finger. Two different vibration exposure dosages were calculated for each individual, i.e. the individual cumulative lifetime dose (mh/s2) or a lifetime 8-h equivalent daily exposure (m/s2).ResultsA significant mean threshold difference was found for all subjects of about 4–5 °C and 1–2 °C in TPTW and TPTC, respectively, between follow-up and baseline. No significant mean difference in TPTC between vibration exposed and non-exposed workers at each occasion could be stated to exist. For TPTW a small but significant difference was found for the right index finger only. Age was strongly related to thermotactile perception threshold. The 8-h equivalent exposure level (A (8)) dropped from about 1.3 m/s2 in 1992 to about 0.7 m/s2 in 2008.ConclusionsA lifetime 8-h equivalent daily exposure to hand-transmitted vibration less than 1.3 m/s2 does not have a significant effect on thermotactile perception. Age, however, has a significant impact on the change of temperature perception thresholds why this covariate has to be considered when using TPT as a tool for health screening.

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials

Background. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established. MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration. Methods. 19 MS patients underwent clinical examination, numerical rating scale (NRS), quantitative sensory testing (QST), and laser-evoked potentials (LEPs) before and after 1 month of therapy. Psychophysiological and neurophysiological data were compared to sex- and age-matched controls. Results. Patients reported a significant reduction in pain. We found statistically significant differences in LEP parameters between patients and controls but no significant change in LEP measures after THC/CBD therapy. Cold and heat detection thresholds were altered in patients but did not change after THC/CBD therapy. There was a significant increase in cold pain threshold by hand stimulation and a significant reduction in abnormal cold perception thresholds. Conclusions. Our results indicate that Sativex® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels.

Correlation of perceptive temperature threshold of oral mucosa and sympathetic skin response

Objectives: To explore the critical values of temperature perception in various mucosa sites of oral cavity and to draw the perceptive temperature threshold maps in healthy volunteers. To observe the interrelationship between subjective cognitive perception and sympathetic skin response (SSR) under various levels of thermal stimuli. Methods: Forty-two healthy volunteers (recruited from the students of Tianjin Medical University, 16 females and 26 males) were enrolled in the present study. The whole oral mucosa of each subject was divided into multiple partitions according to the mucosa type as well as tooth position. Peltier patch (commodity name) semiconductor chip was placed in the central part of each subarea of the mucosa. The stimulus was increased or decreased at 1 ℃ each time from a baseline temperature of 37 ℃. Warm (WT) and cold (CT) perception thresholds were measured thereafter respectively. A topographic temperature map of the oral mucosa for each subject was drew. Furthermore, the SSR was elicited and recorded at three temperature levels of 50 ℃, 55 ℃, 60 ℃ respectively. Analog test with visual analogue scale (VAS) and McGill scales were also performed. Data were statistically analyzed with variance and generalized estimation equation. Results: The tip of the tongue was the most sensitive area with both WT [(38.8±2.1) ℃, P<0.05] and CT [(23.5±4.2) ℃, P<0.05]. The highest heat threshold of gingival mucosa was in the left lower posterior teeth area [(49.9±3.7) ℃, P<0.05], and the highest cold threshold of gingival mucosa was in the left upper posterior teeth area [(15.9±5.5) ℃, P<0.05]. The perceptive temperature threshold increased gradually from the midline to both left and right sides were observed symmetrically and bilaterally. There was no statistically significant differences in temperature perception threshold between males and females [WT, male (44.8±3.1) ℃, female (44.8±3.2) ℃, OR=1.100, P=0.930; CT, Male (18.4±4.9) ℃, female (20.8±4.8) ℃, OR=0.157, P=0.210]. The SSR amplitude at sites of the tongue tip and the lower lip were increased with the rise of temperature [tongue tip (4.58±4.04) mv, P<0.05, lower lip (2.89±3.01) mv, P<0.05]. However, SSR amplitude values had no significant differences between males and females [tongue tip, male (2.00±2.16) mv, female (1.89±1.20) mv, P=0.890; lower lip, male (0.94±0.82) mv, female (0.85±0.68) mv, P=0.887]. Nevertheless, the amplitude of SSR and the VAS score of subjects showed a similar trend. Conclusions: The temperature perception levels were different amongst sites of lip, buccal mucosa, tongue dorsal mucosa and gingival mucosa. SSR amplitude values could reflect the responses of the mouth to the thermal stimuli.

Vibrotactile and thermal perception and its relation to finger skin thickness

ObjectiveQuantitative measurements of vibrotactile and thermotactile perception thresholds (VPT and TPT, respectively) rely on responses from sensory receptors in the skin when mechanical or thermal stimuli are applied to the skin. The objective was to examine if there is a relation between skin thickness (epidermis and dermis) and VPT or TPT. MethodsPerception thresholds were measured on the volar side of the fingertip on 148 male subjects, out of which 116 were manual workers exposed to hand-transmitted vibration and 32 were white-collar (office) workers. Skin thickness was measured using a high-frequency ultrasonic derma scanner system. ResultsThe difference in age, perception thresholds and skin thickness between manual and office workers was small and non-significant except for the perception of cold, which was decreased by vibration exposure. Skin thickness for both subgroups was mean 0.57 mm (range 0.25–0.93 mm). Increased age was associated with decreased perception of warmth and vibration. Lifetime cumulative exposure to vibration, but not age, was associated with decreased perception of cold. ConclusionNo association (p > .05) was found between finger skin thickness in the range of about 0.1–1 mm and vibration perception threshold for test frequencies from 8 to 500 Hz and thermotactile perception thresholds for warmth and cold. Increasing age was associated with reduced perception of vibration and warmth. Vibration exposure was associated with decreased perception of cold. SignificanceSkin thickness is a factor that may affect the response from sensory receptors, e.g., due to mechanical attenuation and thermal insulation. Thus, to evaluate perception threshold measurements, it is necessary to know if elevated thresholds can be attributed to skin thickness. No previous studies have measured skin thickness as related to vibrotactile and thermotactile perception thresholds. This study showed no association between skin thickness and vibrotactile perception or thermotactile perception.

Method-of-limits; Cold and warm perception thresholds at proximal and distal body regions

ObjectiveThermal quantitative sensory testing with the ‘Method-of-Limits’ is an established rationale for detection of small nerve fiber dysfunction, but adequate reference values are crucial for such evaluations, regardless of the underlying cause. This study assessed reference data for cold- (CPT) and warm- (WPT) perception thresholds at both proximal and distal sites in eight body regions of the lower and upper extremities, all determined within the same test session for each subject. MethodsSeventy-five healthy subjects (aged 16–72 years) were tested according to the method-of-limit for CPT and WPT at the dorsum of the foot, the medial and lateral lower leg, the ventral thigh, the thenar eminence, the radial and ulnar part of the lower arm, and the anterior deltoid part of the upper arm. ResultsOverall, thermal perception thresholds (TPT) varied with test location, but were higher in the lower than in the upper part of the body, also WPT were generally higher than CPT. TPT at the dorsum foot highly correlated with age, while inconsistent correlations were noted between TPT and age or height at other tested locations. ConclusionThis study describes for the first time reference values at eight defined body regions, at both proximal and distal sites. SignificanceThe report enables refined evaluations of general small nerve fiber function, as assessed by quantitative thermal sensory testing with the Method-of-Limits.

Effects of transcranial direct current stimulation on temperature and pain perception

Transcranial direct current stimulation modifies cortical excitability and in consequence some cerebral functions. In the present study we aimed to elucidate whether tDCS could affect temperature and pain perceptions in healthy subjects testing different stimulation parameters. A total of 20 healthy subjects were studied by means of quantitative sensory testing. Two different experiments were performed. First, we studied the effects of 15 minutes 2 mA anodal transcranial direct current stimulation applied over left M1 and parietal cortex in two separated sessions. Then, we tested the effects of 5 minutes tDCS over M1 by means of a sham controlled design to optimize the possibility to study minimal effects of tDCS using different polarities (cathodal and anodal) and intensities (1 and 2 mA). 2 mA anodal tDCS, when applied for both 15 and 5 minutes over the motor cortex, increased cold perception threshold. Conversely, motor cortex cathodal tDCS modulated cold perception threshold only when 1 mA intensity was used. M1-tDCS can modify the temperature perception; these effects are polarity and intensity dependent. As stimulation intensity seems critical to determine the effects, we suggest that for clinical application strong anodal tDCS (>1 mA) or weak cathodal tDCS (<2 mA) should be used for pain control.

Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception

It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing.The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle.In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=−0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=−0.506, p=0.0324).Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature.

Small and large fiber neuropathy in those with type 1 and type 2 diabetes: a 5‐year follow‐up study

The purpose of this study was to evaluate progression of diabetic polyneuropathy and differences in the spectrum and evolution of large- and small-fiber involvement in patients with diabetes type 1 and 2 over 5 years. Fifty-nine patients (35 type 1 and 24 type 2) were included. Nerve conduction studies (NCS), quantitative sensory testing, skin biopsy for quantification of intraepidermal nerve fiber density (IENFD), symptom scoring and clinical evaluations were performed. Z-scores were calculated to adjust for the physiologic effects of age and height/gender. Neuropathic symptoms were not significantly more frequent in type 2 than in type 1 diabetic patients at follow-up (54% vs. 37%). The overall mean NCS Z-score remained within the normal range, but there was a small significant decline after 5 years in both groups: type 1 (p = 0.004) and type 2 (p = 0.02). Mean IENFD Z-scores changed from normal to abnormal in both groups, but only significantly in those with type 2 diabetes (reduction from 7.9 ± 4.8 to 4.3 ± 2.8 fibers/mm, p = 0.006). Cold perception threshold became more abnormal only in those with type 2 diabetes (p = 0.049). There was a minimal progression of large fiber neuropathy in both groups. Reduction of small fibers predominated and progressed more rapidly in those with type 2 diabetes.

Quantitative sensory testing in type 1 diabetic patients with painful and painless diabetic neuropathy

The mechanism underlying the development of painful diabetic neuropathy (DN) is unknown. The aim of this study was to compare quantitative sensory testing (QST) characteristics of patients with painful and painless DN and to correlate QST measures with DN pain. Fifty type 1 diabetic patients with DN (30 with painful DN and 20 with painless DN) and 32 age-matched non-diabetic controls were included in this study. For all patients and controls, a detailed assessment of DN was performed which comprised McGill visual analogue scale (McGill VAS) for pain, neuropathy symptom profile and neuropathy disability score (NDS), quantitative sensory testing in form of cold, warm and vibration perception thresholds, nerve conduction studies (NCS), deep-breathing hear rate variability and Neuropad staining scores. Measures of QST, NCS and DB-HRV were correlated with McGill VAS for pain. There were no significant differences in cold, warm and vibration perception thresholds, NCS, DB-HRV and Neuropad scores between patients with painful and painless DN. Cold (r=-0.57, P=0.005), warm (r=0.47, P=0.026) and DB-HRV (r=0.50, P=0.023), however, correlated significantly with McGill VAS scores of pain. In conclusion, Quantitative sensory testing is a helpful tool to identify small nerve fibres damage of DN, correlates with pain intensity but cannot differentiate between painful and painless DN. Both central and peripheral neural injury could be implicated in the genesis of DN pain.

Thermal Quantitative Sensory Testing in Fibromyalgia Patients / Termāla Kvantitatīva Sensora Testēšana Fibromialģijas Pacientiem

Abstract Fibromyalgia (FM) is a chronic disorder manifested by diffuse musculoskeletal pain, fatigue, sleep, and emotional disturbance. The disorder is probably associated with dysfunction of C and A delta peripheral nerve fibres. Thermal quantitative sensory testing (QST) was used to analyse thinly myelinated A delta fibres and nonmylinated C fibres, which function in the nociceptive sensory system, and the spinothalamic pathway. The observation that FM pain has neuropathic nature increased the value of QST as an additional diagnostic tool. The research group included 51 patients. Somatic symptoms were assessed using the Fatigue Severity Score (FSS), Fibromyalgia Impact Questionnaire (FIQ) and American College of Rheumatology (ACR) 2010 year diagnostic criteria. QST was performed by using thermal stimulus at wrist and feet. QST results were compared with 20 non-FM controls matched for age and sex. FM patients showed significant alteration of thermal perception and pain threshold compared with that in healthy controls, which demonstrated possible neuropathic pain nature in FM patients. Changes were more expressed in warm perception and heat pain threshold, which probably indicates that in FM patients C fibres are more damaged and warm perception and warm pain threshold are more sensitive, which may be used as FM diagnostics. We also found statistically significant negative correlations between warm and cold perception thresholds and between heat and cold pain thresholds, reflecting central sensitization or a defective pain inhibitory system.

Discriminative validity of sensory evaluation in a whiplash-associated disorder II population

Aim: Evidence suggests chronic whiplash is associated with sensory hypersensitivity. Understanding the degree of sensory impairment could enhance rehabilitation strategies. This preliminary study determined whether differences in sensory evaluation occur post whiplash injury. Methods: Single-blinded, case control observational study using a convenience sample of 20 participants (median age 28.5 years, low disability) with chronic grade II whiplash-associated disorder (CWADII) and 22 control participants (median age 26 years) with no history of whiplash/neck injury. Outcome measures included vibration and cold pain perception threshold, and joint position error. Results: Significant associations using Kendall's tau correlation coefficient were found between: vibration thresholds (thenar and hypothenar eminences) for the CWADII group (p&lt;0.01); cold pain thresholds (thenar, 5th metacarpophalangeal, mid cervical spine) in both groups (p&lt;0.01); joint positioning errors (global positioning following right/left rotations, left rotation/extension) (p&lt;0.01) in the CWADII group; and between vertical direction errors (following right/left rotation) in both groups (p&lt;0.01). Discrimination between groups was not identified using separate logistic regressions on vibration or cold pain thresholds (thenar eminence) or on global flexion/extension/right rotation position errors (p&gt;0.01). Conclusions: The findings do not support the use of vibration, cold pain threshold or joint position error to identify individuals with CWADII with low disability.