Age Differences in Multimodal Quantitative Sensory Testing and Associations With Brain Volume

Examining somatosensory function by age, testing site, and modality

An investigation of gender-dependent perception of thermal and pain: a quantitative sensory testing study

To compare somatosensory function profiles and psychologic factors in patients with primary burning mouth syndrome (BMS) and healthy controls and to evaluate correlations of subjective pain ratings with somatosensory and psychologic parameters. A quantitative sensory testing (QST) protocol-including cold detection threshold (CDT), warmth detection threshold (WDT), thermal sensory limen (TSL), paradoxical heat sensation (PHS), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT)-was performed at the oral mucosa of the tongue, buccal, and palatal sites in 30 Chinese patients (25 women and 5 men, mean age 50.9 ± 9.2 years) with primary BMS and in 18 age- and gender-matched healthy controls (15 women and 3 men, mean age 53.2 ± 7.0 years). For each BMS patient, z scores and loss/gain scores were computed. Psychologic status was evaluated in both groups using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Correlations of BMS patients' subjective pain ratings with somatosensory and psychologic profiles were assessed with the use of Pearson or Spearman correlations and multiple linear regression. In BMS patients, 53.3% had somatosensory abnormalities according to z scores vs 22.2% of healthy controls (P = .033). The abnormalities in BMS patients were somatosensory loss to thermal nonnoxious stimuli (TSL = 20.0%, CDT = 13.3%, WDT = 13.3%), mechanical pressure stimuli (PPT = 16.7%), pinprick stimuli (MPT = 6.7%), and thermal pain stimuli (CPT = 3.3%), and somatosensory gain to repetitive pinprick stimuli (WUR = 6.7%), pressure stimuli (PPT = 6.7%), and thermal pain stimuli (HPT = 3.3%). The most frequent loss/gain score was 13.3% for loss of thermal somatosensory function with no somatosensory gain; 13.3% for loss of thermal and mechanical somatosensory function with no somatosensory gain; and 13.3% for gain of mechanical somatosensory function with no somatosensory loss. Mild elevations in anxiety scores were seen in 30% of the BMS patients, and 50% and 36.7% had mild and moderate elevations, respectively, in depression scores. No anxiety or depression was detected in the control group. QST results, but not psychologic scores, were significantly correlated with patients' subjective pain ratings (PHS, Spearman coefficient -0.384, P = .029; CPT, Pearson coefficient -0.370, P = .034; MPT, Pearson coefficient -0.376, P = .032; PPT, Pearson coefficient 0.363, P = .037). The present findings documented distinct differences in somatosensory function in patients with primary BMS compared to controls, indicating a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic functioning.

Somatosensory changes after sagittal split ramus osteotomy (SSRO) have not been fully studied in Chinese patients by the latest technologies. To provide a comprehensive analysis of somatosensory function at the lower lip and chin at different time points following SSRO in a Chinese population. A total of 22 patients (18-27years; nine men) with skeletal III malocclusion and scheduled for SSRO were recruited. Quantitative sensory testing (QST) was performed at pre-operation (baseline), 1week (1W), 1, 3 and 6months (1M, 3M, 6M) post-operatively. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT), mechanical pain threshold (MPT), pressure pain threshold (PPT) and two-point discrimination threshold (2PD) were tested at the lower lip and chin. Except for PPT at both test sides at 1W and 1M, all QST values indicated a significantly reduced sensitivity (p<.05). All values had returned to baseline values at 3M with exception of HPT at the right chin which, however, had recovered at 6M (p>.05). Somatosensory function at the lower lip and chin appears to be fully recovered in the majority of young Chinese adults 6months after SSRO for skeletal class III malocclusion.

In order to distinguish the grades of breast pain with a quantitative index, the detection and pain thresholds were measured with the technique of TSA (Thermal Sensory Analysis) on patients with breast pain. We aimed to explore whether TSA could be used to predicate the degree of breast pain as an objective indicator or not. Thirtytwo female outpatients with breast pain were included in the study by inclusion criteria. A total of sixtyfour breasts were measured. The cold pain threshold (CPT), cold detection threshold (CDT), warm detection threshold (WDT) and heat pain threshold (HPT) were measured at the following five points of both sides: neck, shoulder, axilla, back and super ior lateral quadrant of breast. The sixtyfour breasts were devided into three groups: Group A consisted of 29 breasts that have breast pain grade from 0 to 1 (No pain at that time); Group B consisted of 20 breasts that have breast pain grade from 2 to 4 (Pain exist, but participant can’t give it an explicit score); Group C consisted of 15 breasts that have breast pain grade from 5 to 7. Statistic analysis was performed by SPSS 20.0 to compare the means and SD. Variance for each threshold at each site was expressed as Coefficient of Variation percentage (CV%), using the standard deviation (SD) divided by the meanx100. On every sites, group B has the highest value of WDT and HPT. And expect the site of axilla, group C has higher values than group A of WDT and HPT. On the site of breast, the values of CPT and CDT have the trend to increase from group A to group C. But the differences in groups were without statistically significant differences (p>0.2). The CV% of HPT and WDT are lowest and near to each other, and CPT has the highest value of CV%. Breast pain can not only reduce the sensibility of warm detection and heat pain of breast, but also the sites close to breast. Oppositely, breast pain can enhance the sensibility of cold detection and cold pain of breast. But C PT has the highest value of CV%, this may means CPT has poor reliability due to wide variance.

Background: Many patients referred for physical therapy have pain and somatosensory problems. Thermal quantitative sensory testing (QST) is used for assessing somatosensory function. Method of limits (MLI) and method of levels (MLE) are two commonly measurement methods used for thermal QST. A good measurement method for clinical application should be convenient and reliable. The purpose of this study was to compare the acceptability and reliability of the MLI and MLE. Methods: Twenty-eight healthy adults (14 males and 14 females) participated in a thermal QST test retest study. The types of the thermal QSTs included the Cold Detection Threshold (CDT), Warm Detection Threshold (WDT), Cold Pain Threshold (CPT), and Heat Pain Threshold (HPT). Participants were examined with thermal QST using the two methods (MLI and MLE), and then re-examined after one week. Both the relative reliability and absolute reliability were estimated. Results: The acceptability was better in the MLI than in the MLE. Many trials of the MLE was needed (the mean number of trials = 12.2; range from 7 to 27 trials). The relative reliability of the MLI and MLE were similar; the range of intraclass correlation coefficient were 0.65 to 0.88 and 0.69 to 0.86 for the MLI and MLE, respectively. However, the absolute reliability of the CDT, WDT, and HPT on the MLE were not as accurate as those on the MLI. Conclusion: When we compared the acceptability and reliability, the MLI was superior to the MLE. The MLI is recommended as useful method for measuring thermal and pain thresholds.

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12–33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm–2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.

Subthalamic deep brain stimulation modulates small fiber–dependent sensory thresholds in Parkinson’s disease

BackgroundSomatosensory profiling in affected and non-affected body regions can strengthen our insight regarding the underlying pain mechanisms, which can be valuable in treatment decision making and to improve outcomes, in patients with degenerative lumbar spine disorders pre-surgery. The aim was to describe somatosensory profiles in patients with degenerative lumbar spine disorders, to identify the proportion with altered somatosensory profile, and to analyze demographic characteristics, self-reported function, pain, and health pre- and 3 months post-surgery.MethodsIn this prospective cohort study in a Spine Clinic, 105 patients scheduled for surgery for spinal stenosis, disc herniation, degenerative disc disease, or spondylolisthesis were consecutively recruited. Exclusion criteria were; indication for acute surgery or previous surgery at the same spinal level or severe grade of pathology. Quantitative sensory testing (QST) and self-reported function, pain, and health was measured pre- and 3 months post-surgery. The somatosensory profile included cold detection threshold, warmth detection threshold, cold pain threshold, heat pain threshold and pressure pain threshold in affected and non-affected body regions.ResultsOn a group level, the patients’ somatosensory profiles were within the 95% confidence interval (CI) from normative reference data means. On an individual level, an altered somatosensory profile was defined as having two or more body regions (including a non-affected region) with QST values outside of normal ranges for reference data. The 23 patients (22%) with altered somatosensory profiles, with mostly loss of function, were older (P = 0.031), more often female (P = 0.005), had higher back and leg pain (P = 0.016, 0.020), lower mental health component summary score (SF-36 MCS) (P = 0.004) and larger pain distribution (P = 0.047), compared to others in the cohort. Post-surgery there was a tendency to worse pain, function and health in the group with altered somatosensory profile pre-surgery.ConclusionsOn a group level, patients with degenerative lumbar spine disorders scheduled for surgery were within normal range for the QST measurements compared to reference values. On an individual level, an altered somatosensory profile outside of normal range in both affected and non-affected body regions occurred in 22% of patients, which may indicate disturbed somatosensory function. Those patients had mostly loss of sensory function and had worse self-reported outcome pre-surgery, compared to the rest of the cohort. Future prospective studies are needed to further examine whether these dimensions can be useful in predicting post-surgery outcome and guide need of additional treatments.

ABSTRACTBackground and AimsSkin biopsies are the primary diagnostic test for small fiber neuropathy, but recently corneal confocal microscopy (CCM) has been developed as an alternative. We compared the correlations of each of these morphometric assessments with peripheral nerve function evaluated through comprehensive quantitative sensory testing (QST) in a mixed etiology polyneuropathy cohort.MethodsCCM and skin biopsies were performed in a prospective cohort of unselected patients undergoing polyneuropathy diagnostic work‐up. We used predefined criteria to identify patients with small or mixed fiber neuropathy. The correlations between corneal nerve fiber density (CNFD), fiber length (CNFL), branch density (CNBD), and tortuosity (CNFT) and the intraepidermal nerve fiber density (IENFD) at the distal leg and the results of QST at the foot were determined.ResultsTwo‐hundred and forty‐four patients were included in the analysis. CNFD was negligibly correlated with warm detection threshold (WDT) (r = −0.15; p = 0.023), while there was no statistically significant correlation with other QST measures. There were no statistically significant correlations between neither CNFL nor CNBD and any of the QST measures. CNFT correlated negligibly with WDT (r = 0.17; p = 0.008) and vibration detection threshold (VDT) (r = −0.13; p = 0.044). IENFD correlated moderately with WDT (r = −0.33; p < 0.0001) and mechanical pain threshold (r = −0.37; p < 0.0001) and weakly with cold detection threshold (r = 0.21; p = 0.0008), mechanical detection threshold (r = −0.21; p = 0.0008) and VDT (r = 0.23; p = 0.0004).InterpretationIENFD correlated better with small and large fiber function at the foot than CCM measures in patients with mixed etiology polyneuropathy. Longitudinal studies are needed to assess the clinical utility for neuropathy progression.

The variability in thermal threshold-assessments in post-thoracotomy pain syndrome

Topical high-dose capsaicin acting on TRPV1 receptors and inducing an intraepidermal decrease in the small nerve fibre count is effective in treating neuropathic pain (NP). Sensory changes after capsaicin application, their correlation with pain relief and their role as possible predictors of response have been insufficiently analysed. We hypothesized a positive correlation between pain relief and increase in the warmth detection threshold (WDT), indicating loss of C-fibre function, and higher response rates in patients with preserved C-fibre function or heat hyperalgesia before application. Quantitative Sensory Testing (DFNS protocol) was conducted in 20 unilaterally treated patients with peripheral NP (peripheral nerve injury: n = 14, polyneuropathy: n = 4, postherpetic neuralgia: n = 2) before and 2, 4, 6 and 8 weeks after application of capsaicin (8%) in this open-label study. Response was defined as ≥30% or ≥2 (Numeric Rating Scale: 0-10) decrease of current pain at any follow-up compared to baseline. In all patients, WDT significantly increased 8 weeks after capsaicin application, but did not correlate with pain relief in responders (n = 10, r = 0.179, p = 0.141). Before treatment, responders showed significantly higher z-values for the cold (CPT, +0.7 ± 1.1 vs. -0.4 ± 0.9) and mechanical pain threshold (MPT; 0.7 ± 2.5 vs. -1.2 ± 1.3), but did not differ from non-responders regarding WDT or heat pain threshold. A sum of the z-values for CPT and MPT >0.8 before treatment identified responders with 100% specificity and 70% sensitivity. Efficacy of capsaicin does not correlate with the induced loss of function of small fibres, measured by QST. Presence of cold and pinprick hyperalgesia seems to be predictive of response to capsaicin (8%).

Digital nerve lacerations are common. Current methods employed to differentiate intact and transected digital nerves lack diagnostic accuracy. This may result in patients with intact nerves undergoing unnecessary surgery. The objective of the study was to determine the best diagnostic method for detecting true sensory nerve transections and to delineate the sensitivities and specificities of common sensory tests. Patients aged 18-65 years with suspected complete digital nerve lacerations were recruited. Sensory testing including static two-point discrimination (s2PD), Semmes-Weinstein Monofilaments, and Quantitative Sensory Testing were used prior to surgical exposure to evaluate different categories of sensory nerve fibers. Likelihood ratios, sensitivity, and specificity of each test were compared to direct visualization intraoperatively. Receiver operating characteristic (ROC) curves were used to determine the area under the curve (AUC) for each test. Of the 60 patients recruited, 41 (68%) had complete digital nerve transections while 19 (32%) had intact nerves. Heat pain threshold testing showed the greatest AUC at 0.812 ± 0.067 with a sensitivity of 90% and specificity of 65% at a cutoff of 22.1 just noticeable difference (JND). However, combining s2PD (7 mm, 100% sensitivity, 32% specificity) and warm detection threshold (WDT) (25 JND, 100% sensitivity, 37% specificity) in a two-step algorithm achieved 100% sensitivity and increased the specificity to 58%. Implementing a two-step diagnostic algorithm combining s2PD and WDT can effectively diagnose complete digital nerve laceration with high sensitivity and improved specificity. These findings underscore the utility of both tests in accurately identifying complete digital nerve lacerations.

The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. Sixteen healthy subjects (8 males, mean age 27±5years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15μg) on one thigh and electrical current stimulation (ES, 1Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin® , 25MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26±3years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin. BoNT/A reduced the 1Hz ES flare size (p<0.001) and pain ratings (p<0.01), but had no effect on 4Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2°C, p<0.001; HPT Δ 1.8°C, p<0.005). BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin. The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.

This study aimed to investigate the role of cutaneous vasodilation in heat pain tolerance during aging. We hypothesized that reduced vasodilation in response to heat would lead to a less efficient heat dissipation, and thus be associated with diminished heat pain tolerance. Due to their efferent role in vasomotor function, we hypothesized that C-fiber functionality would be associated to the efficacy of cutaneous vasodilation. Twenty younger and forty older subjects participated in a 15-min heat pain tolerance test, during which pain ratings were continuously measured, along with skin temperature. Participants could terminate the test at any time if the pain became unbearable. A local thermal hyperemia protocol was conducted to assess cutaneous vasodilation using laser Doppler flowmetry. Warm detection and heat pain thresholds were measured to evaluate small fiber functionality. Older subjects were divided into two groups according to their pain tolerance duration. The older MAX group (n=22; i.e., 55%) completed the tolerance test, while the older LOW group did not. Older MAX had preserved cutaneous vasodilation compared to young subjects, whereas older LOW had reduced heat-induced vasodilation. In addition, the skin temperature of older LOW subjects reached a higher level during the pain tolerance test, which was associated to higher pain ratings compared to the two other groups. Older LOW also had higher warm detection threshold, pointing to diminished C-fiber functionality. Reduced cutaneous vasodilation, possibly linked to impaired C-fiber functionality in aging, affects heat pain tolerance due to less efficient heat dissipation.