Quantitative Sensory Testing Assessments Research Articles

Pain Catastrophizing Moderates the Relationship Between Pain Sensitivity and Clinical Pain in Adolescents With Functional Abdominal Pain

Pain catastrophizing has been linked to amplified pain sensitivity assessed using quantitative sensory testing (QST) in adults; pediatric data are limited, particularly in youth with functional abdominal pain (FAP). With increasing use of QST to evaluate somatosensory function and predict pain outcomes, we examined the associations between QST and clinical pain in adolescents with FAP and tested the moderating effects of pain catastrophizing. Seventy-seven adolescents (mean age 16.6 years, 85.7% female, 72.7% White, 90.8% non-Hispanic) who fulfilled diagnostic criteria for FAP completed QST assessment (pressure pain threshold and tolerance, heat pain threshold, conditioned pain modulation) and measures of abdominal pain intensity, pain interference, and pain catastrophizing. Adjusting for age and sex, only higher heat pain threshold was associated with higher abdominal pain intensity (Beta per 1-standard deviation = .54, P = .026). Contrary to hypothesis, for youth with higher pain catastrophizing, higher pressure pain tolerance was associated with greater abdominal pain intensity, but associations were not significant for youth with lower catastrophizing (P = .049). Similarly, for those with higher pain catastrophizing (in contrast to lower pain catastrophizing), higher pressure pain thresholds and tolerance were associated with higher pain interference (P = .039, .004, respectively). Results highlight the need to investigate the influence of pain catastrophizing on QST. PerspectiveThis study demonstrated unexpected findings of pain catastrophizing moderating the relationships between pressure pain threshold and tolerance, and clinical pain in adolescents with FAP. This raised questions regarding our understanding of psychological contributions to QST findings in pediatric populations with chronic pain.

Botulinum toxin-A effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: a randomized double-blind clinical trial

The antinociceptive effect of BoNT-A have been well documented in animal studies; however, results of few but well-designed randomized placebo-controlled clinical trials about BoNT-A efficacy in masticatory myofascial pain (MFP) are inconsistent. Therefore, the present randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of BoNT-A in patients with refractory MFP. Twenty-eight patients with pain reduction of less than 30% despite conservative treatment and with an average pain intensity of > 50 mm on the visual analogue scale (VAS) participated. Patients were randomly assigned to receive a total of 80 U of BoNT-A or saline solution (SS) injected into the masseter and anterior temporalis muscles. Pain intensity (VAS), quantitative sensory testing (QST), conditioned pain modulation (CPM), and psychosocial status were examined. Follow-up was performed at 1 and 6 months. For repeated-measure comparisons between evaluation times, Friedman test with Bonferroni correction was used for pain and somatosensory variables and the Wilcoxon test for the psychosocial variables. The Mann–Whitney test was used for all comparisons between groups. The BoNT-A group had a significant decrease in pain intensity at follow-ups compared with the SS group (p < 0.001). QST assessment revealed higher pressure pain threshold values in the masseter muscle for BoNT-A group compared to SS (p < 0.03) at all follow-ups. No differences were found for mechanical pain threshold and wind-up ratio values (p > 0.05) in the entire study. The BoNT-A group presented the most efficient CPM effect (p < 0.03) only at the 1 month follow-up in the masseter muscle. There was a significant time effect for BoNT-A in all psychosocial variables (p < 0.05) and a drug effect in the Central Sensitization Inventory (p < 0.01), Pittsburgh Sleep Quality Index (p < 0.004), and Healthy Survey 36 (p < 0.05) at 6 months follow-up. The study demonstrates that a single injection-session of BoNT-A has positive effects on the hall pain spectrum of patients with refractory masticatory myofascial pain.

Chronic post-thoracotomy pain after lung cancer surgery: a prospective study of preoperative risk factors.

The objective of this longitudinal cohort study was to investigate if preoperative pain mechanisms, anxiety, and depression increase risk of developing chronic post-thoracotomy pain (CPTP) after lung cancer surgery. Patients with suspected or confirmed lung cancer undergoing surgery by either video-assisted thoracoscopic surgery or anterior thoracotomy were recruited consecutively. Preoperative assessments were conducted by: quantitative sensory testing (QST) (brush, pinprick, cuff pressure pain detection threshold, cuff pressure tolerance pain threshold, temporal summation and conditioned pain modulation), neuropathic pain symptom inventory (NPSI), and the Hospital Anxiety and Depression Scale (HADS). Clinical parameters in relation to surgery were also collected. Presence of CPTP was determined after six months and defined as pain of any intensity in relation to the operation area on a numeric rating scale form 0 (no pain) to 10 (worst pain imaginable). A total of 121 patients (60.2 %) completed follow-up and 56 patients (46.3 %) reported CPTP. Development of CPTP was associated with higher preoperative HADS score (p=0.025), higher preoperative NPSI score (p=0.009) and acute postoperative pain (p=0.042). No differences were observed in relation to preoperative QST assessment by cuff algometry and HADS anxiety and depression sub-scores. High preoperative HADS score preoperative pain, acute postoperative pain intensity, and preoperative neuropathic symptoms were was associated with CPTP after lung cancer surgery. No differences in values of preoperative QST assessments were found. Preoperative assessment and identification of patients at higher risk of postoperative pain will offer opportunity for further exploration and development of preventive measures and individualised pain management depending on patient risk profile.

Outcomes of a QST Protocol in Healthy Subjects and Chronic Pain Patients: A Controlled Clinical Trial.

Chronic pain is an important cause of disability with a high burden to society. Quantitative sensory testing (QST) is a noninvasive multimodal method used to discriminate the function of nerve fibers. The aim of this study is to propose a new, reproducible, and less time-consuming thermal QST protocol to help characterize and monitor pain. Additionally, this study also compared QST outcomes between healthy and chronic pain subjects. Forty healthy young/adult medical students and fifty adult/elderly chronic pain patients were evaluated in individual sessions including pain history, followed by QST assessments divided into three proposed tests: pain threshold, suprathreshold, and tonic pain. In the chronic pain group, a significantly higher pain threshold (hypoesthesia) and a higher pain sensibility (hyperalgesia) were demonstrated at threshold temperature when compared to healthy participants. The sensitivity to the suprathreshold and tonic stimulus did not prove to be significantly different between both groups. The main results demonstrated that the heat threshold QST tests can be helpful in evaluating hypoesthesia and that the sensitivity threshold temperature test can demonstrate hyperalgesia in individuals with chronic pain. In conclusion, this study demonstrates the importance of using tools such as QST as a complement to detect changes in several pain dimensions.

The Role of Quantitative Sensory Testing in Clinical Medicine and Research

A healthy peripheral nervous system allows for perception of temperature, touch and vibration at normal levels of stimulation without hypersensitivity or pain and is a key determinant of quality of life. Quantitative sensory testing (QST) describes an array of noninvasive methods for quantifying sensory function and monitoring sensory loss among patients with or at-risk for peripheral neuropathy (PN). Like audiometry, QST quantifies patients’ subjective sensory experience with instrumentation that is precise and amenable to serial use. Thermal QST is the only diagnostic technology able to detect and quantify preclinical sensory deficit via direct patient feedback and merits wider use in clinical practice and research. A comprehensive QST assessment of 13 sensory parameters may be performed in an hour or less; abbreviated assessments take substantially less time. Although increasingly employed to evaluate sensation, define pain phenotypes, and predict outcomes in research studies and to monitor neurologic deficits in clinical practice, QST remains undervalued and underutilized possibly due to limited familiarity, experience, and understanding within the medical community and a lack of published standards regarding its use. This article is intended as a concise QST overview (with a focus on the use of thermal QST for the detection of small fiber abnormalities often associated with early PN) aimed at improving awareness of the unique role of QST in evaluating sensory function

Identifying Predictors of Referred Pain, an Experimental Model of Nociplastic Pain

In clinical populations, it can be challenging to identify the underlying mechanisms of chronic pain. Referred pain (RP) from an intramuscular infusion provides a clinically-relevant model of centrally-mediated pain that can be used to investigate factors contributing to nociplastic pain. Further, quantitative sensory testing (QST) is commonly used to assess for central mechanisms. However, it is challenging to validate QST assessments in humans. Thus, the primary purpose of this study was to characterize predictors of RP incidence, including local pain, sex, and multiple QST assessments: pain thresholds (PTs), temporal summation (TS), and conditioned pain modulation (CPM) using heat, pressure and punctate stimuli. 312 adults (162F) completed 4 experimental pain conditions at 2 visits: intramuscular anterior tibialis infusion of acidic (pH 5.2) or normal saline at 40 and 80 ml/hr for 5 min (blocked order). Ankle RP was assessed as pain >1/10. 200 participants also completed a 3rd visit involving the QST. Local and RP increased on average across the 4 conditions. Generalized logit modeling (R) with random slopes and intercepts, and adjustment for age, BMI, negative affect, and infusion condition were used to compute odds ratios (OR). RP incidence increased 5.33 times (OR+/-1.34 SEM, p<0.001) with each 1/10 increase in local pain overall. Women were 5.35 times more likely than men to have RP (OR+/-1.91, p=0.01) overall. Of the multiple QST assessed, only one was a significant predictor; RP was 11.47 times more likely when pressure TS was present (OR+/-2.49, p=0.008). No other QST significantly predicted presesnce of RP. Although various QST have been used as indicators of nociplastic pain in clinical populations, these results suggest that they are not interchangeable. Thus, it may not be valid to use all forms of QST as equivalent metrics for the presence/absence of central pain mechanisms in clinical pain conditions. Grant support from NIAMS R03AR065197.

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.

Development of a Novel Brief Quantitative Sensory Testing Protocol That Integrates Static and Dynamic Pain Assessments: Test-Retest Performance in Healthy Adults

Quantitative sensory testing is an expanding pain research domain with numerous clinical and research applications. There is a recognized need for brief reliable quantitative sensory testing protocols that enhance assessment feasibility. This study aimed to integrate static (pain threshold, tolerance, suprathreshold) and dynamic (conditioned pain modulation, offset analgesia, temporal summation) pain reactivity measures into a brief 20-minute protocol that uses a single portable device. The test-retest performance of this optimized protocol was evaluated. Using a test-retest design, the brief quantitative sensory testing assessment was administered to participants on two occasions separated by exactly 7 days. A clinical psychology research laboratory at Syracuse University. Participants were 33 healthy adults recruited from Syracuse University's online research participation pool. A portable computerized quantitative sensory testing device delivered contact-heat pain to assess static and dynamic pain measures in participants. Dynamic responses were continuously recorded using a computerized visual analog scale. Pain threshold, tolerance, and suprathreshold exhibited excellent reliability (intraclass correlations ranged from 0.80 to 0.83). Conditioned pain modulation, offset analgesia, temporal summation yielded reliability in the good to excellent range (intraclass correlations ranged from 0.66 to 0.71). Findings suggested that this brief integrated QST protocol may reliably monitor human pain reactivity over brief periods. This protocol may enhance quantitative sensory testing feasibility in clinical and research settings.

Severe Pain in Chronic Pancreatitis Patients: Considering Mental Health and Associated Genetic Factors.

Pain is the most distressing and disruptive feature of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) resulting in low quality of life (QOL) and disabilities. There is no single, characteristic pain pattern in patients with RAP and CP. Abdominal imaging features of CP accurately reflect morphologic features but they do not correlate with pain. Pain is the major driver of poor quality of life (QOL) and it is the constant pain, rather than intermittent pain that drives poor QOL. Furthermore, the most severe constant pain experience in CP is also a complex condition. The ability to target the etiopathogenesis of severe pain requires new methods to detect the exact pain mechanisms in an individual at cellular, tissue, system and psychiatric levels. In patients with complex and severe disease, it is likely that multiple overlapping mechanisms are simultaneously driving pain, anxiety and depression. Quantitative sensory testing (QST) shows promise in detecting alterations in central processing of pain signals and to classify patients for mechanistic and therapeutic studies. New genetic research suggests that genetic loci for severe pain in CP overlap with genetic loci for depression and other psychiatric disorders, providing additional insights and therapeutic targets for individual patients with severe CP pain. Well-designed clinical trials that integrate clinical features, QST, genetics and psychological assessments with targeted treatment and assessment of responses are required for a quantum leap forward. A better understanding of the context and mechanisms contributing to severe pain experiences in individual patients is predicted to lead to better therapies and quality of life.

Quantitative Sensory Testing Discriminates Central Sensitization Inventory Scores in Participants with Chronic Musculoskeletal Pain: An Exploratory Study.

The Central Sensitization Inventory (CSI) is often used in clinical settings to screen for the presence of central sensitization. However, various cutoff scores have been reported for this tool, and scores have not been consistently associated with widespread pain sensitivity as measured with quantitative sensory testing (QST). The purpose of this study was to compare QST profiles among asymptomatic controls and participants with chronic musculoskeletal pain (CMP), and to determine the association between self-report questionnaires and QST in participants with CMP. Twenty asymptomatic controls and 46 participants with CMP completed the CSI, PROMIS-29, and QST assessments of mechanical and thermal pain thresholds remote to the area of pain. Receiver Operating Characteristic analysis revealed a cutoff score of 33.5 for the CSI. PROMIS-29 Quality of Life (QOL) inventory and QST measures were compared between low and high CSI groups. The high CSI group (n=19) had significantly lower mechanical and thermal pain thresholds, and larger impairments in QOL measures, compared to the low CSI group (n=27) and asymptomatic controls. Participants with CSI scores <33.5 presented similarly to asymptomatic controls. Anxiety, pain interference, and CSI scores demonstrated the highest number of significant associations to QST measures. A cutoff score of 33.5 on the CSI may be useful for discriminating widespread pain sensitivity and quality of life impairments in participants with CMP. Future studies should consider how the presence of high or low CSI may impact differential diagnosis, prognosis, and treatment responsiveness for patients with primary or secondary CMP.

Preoperative quantitative sensory testing and robot-assisted laparoscopic hysterectomy for endometrial cancer: can chronic postoperative pain be predicted?

Objectives Chronic postoperative pain is prevalent after robot-assisted laparoscopic hysterectomy for endometrial cancer. Preoperative Quantitative Sensory Testing (QST) has been utilized to identify patients at risk of developing chronic postoperative pain after a range of surgical procedures. The aim of this prospective, observational study was to (1) determine the prevalence of chronic postoperative pain, (2) assess selected preoperative risk factors for chronic postoperative pain, and (3) evaluate if preoperative QST profiling could predict the development of chronic postoperative pain following robot-assisted laparoscopic hysterectomy for endometrial cancer. Methods One-hundred and sixty consecutive patients were included and handheld pressure algometry, cuff pressure algometry, temporal summation of pain, conditioned pain modulation, and heat pain thresholds were assessed prior to surgery. Patients were asked to fill out a questionnaire concerning pain in the pre- and post-operative time period six months after surgery. Chronic postoperative pain was defined as persistent, moderate to severe pain (mean visual analogue scale (VAS)≥3) on a daily basis six months after surgery. Results The prevalence of chronic postoperative pain after robot-assisted laparoscopic hysterectomy for endometrial cancer was of 13.6% (95% CI 8.4-20.4%). Patients that would develop chronic postoperative pain had a lower BMI (p=0.032), a higher prevalence of preoperative pelvic pain (p<0.001), preoperative heat pain hyperalgesia (p=0.043) and a higher level of acute postoperative pain (p<0.001) when compared to patients that would not develop chronic postoperative pain. A logistic regression model demonstrated that the presence of preoperative pelvic pain was a significant, independent predictive risk factor for development of chronic postoperative pain (OR=6.62, 95% CI 2.26-19.44), whereas none of the QST parameters could predict postoperative pain. Conclusions Preoperative QST assessment could not predict the development of chronic postoperative pain despite preoperative heat pain hyperalgesia in patients that would develop chronic postoperative pain.

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.

A clinically feasible method for the assessment and characterization of pain in patients with chronic pancreatitis

Background and aimsPain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST). MethodsThis was a cross-sectional, multicenter study of 122 control subjects without pancreatic disease and another 60 patients with painful CP. All subjects underwent standardized QST assessments including a cold pressor test, a conditioned pain modulation paradigm, repetitive pin-prick stimuli (temporal summation) and pressure stimulation of the upper abdominal (pancreatic) and control dermatomes. The effects of age and gender on QST assessment parameters were investigated and normative reference values based on quartile regression were derived and implemented in algorithms to categorize patients according to their patterns of central pain processing (normal vs. segmental sensitization vs. widespread sensitization). ResultsAbsolute pressure thresholds were subject to clinically relevant gender effects (all p < 0.001), while the remainder of QST parameters were unaffected by age and gender. The algorithm with the best discriminatory capacity showed good separation between patients and controls (p < 0.001); 50% of patients had normal central pain processing, 23% had evidence of segmental sensitization and 27% had evidence of widespread sensitization. ConclusionWe show normative reference values for a clinically feasible method for assessment and characterization of pain mechanisms in patients with CP. Application of this method streamlines the evaluation of pancreatic pain and may be used to inform treatment. Clinicaltrials.gov idNCT03434392.

Structural Brain Alterations Before and After Total Knee Arthroplasty: A Longitudinal Assessment.

Many studies have provided evidence of altered brain structure in chronic pain conditions, as well as further adaptations following treatment that are coincident with changes in pain. Less is known regarding how these structural brain adaptations relate to assessments of nociceptive processing. The current study aimed to investigate brain structure in people with knee osteoarthritis (OA) before and after total knee arthroplasty (TKA) and to investigate the relationships between these findings and quantitative sensory testing (QST) of the nociceptive system. Twenty-nine people with knee OA underwent magnetic resonance imaging (MRI) scans and QST before and six months after TKA and were compared with a pain-free control group (N = 18). MRI analyses involved voxel-based morphometry and fractional anisotropy. Before TKA, there was reduced gray matter volume and impaired fractional anisotropy in areas associated with nociceptive processing, with further gray matter adaptations and improvements in fractional anisotropy evident after TKA. QST revealed increased nociceptive facilitation and impaired inhibition in knee OA that was reversed after TKA. There were minimal relationships found between MRI data and QST assessments or pain report. In people with end-stage knee OA, region-specific gray matter atrophy was detected, with further changes in gray matter volume and improvements in white matter integrity observed after joint replacement. Despite coincident alterations in nociceptive inhibition and facilitation processes, there did not appear to be any association between these functional assessments of the nociceptive system and changes in brain structure.

Psychosocial factors partially mediate the relationship between mechanical hyperalgesia and self-reported pain.

Amplification of sensory signalling within the nervous system along with psychosocial factors contributes to the variation and severity of knee pain. Quantitative sensory testing (QST) is a non-invasive test battery that assesses sensory perception of thermal, pressure, mechanical and vibration stimuli used in the assessment of pain. Psychosocial factors also have an important role in explaining the occurrence of pain. The aim was to determine whether QST measures were associated with self-reported pain, and whether those associations were mediated by psychosocial factors. Participants with knee pain identified from a population-based cohort completed a tender point count and a reduced QST battery of thermal, mechanical and pressure pain thresholds, temporal summation, mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA) and vibration detection threshold performed following the protocol by the German Research Network on Neuropathic Pain. QST assessments were performed at the most painful knee and opposite forearm (if pain-free). Participants were asked to score for their global and knee pain intensities within the past month (range 0-10), and complete questionnaire items investigating anxiety, depression, illness perceptions, pain catastrophising, and physical functioning. QST measures (independent variable) significantly correlated (Spearman's rho) with self-reported pain intensity (dependent variable) were included in structural equation models with psychosocial factors (latent mediators). Seventy-two participants were recruited with 61 participants (36 women; median age 64 years) with complete data included in subsequent analyses. Tender point count was significantly correlated with global pain intensity. DMA at the knee and MPS at the most painful knee and opposite pain-free forearm were significantly correlated with both global pain and knee pain intensities. Psychosocial factors including pain catastrophising sub-scales (rumination and helplessness) and illness perceptions (consequences and concern) were significant partial mediators of the association with global pain intensity when loaded on to a latent mediator for: tender point count [75% total effect; 95% confidence interval (CI) 22%, 100%]; MPS at the knee (49%; 12%, 86%); and DMA at the knee (63%; 5%, 100%). Latent psychosocial factors were also significant partial mediators of the association between pain intensity at the tested knee with MPS at the knee (30%; 2%, 58%), but not for DMA at the knee. Measures of mechanical hyperalgesia at the most painful knee and pain-free opposite forearm were associated with increased knee and global pain indicative of altered central processing. Psychosocial factors were significant partial mediators, highlighting the importance of the central integration of emotional processing in pain perception. Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain.

Multicenter assessment of quantitative sensory testing (QST) for the detection of neuropathic-like pain responses using the topical capsaicin model

ABSTRACT Background The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers. Aim The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers. Methods A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic. Results Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain (P < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT. Conclusion These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses.

3. Conditioned pain modulation paradigm in normal subjects

Conditioned pain modulation (CPM) is an experimental paradigm used to assess the endogenous pain inhibition mechanisms. In CPM paradigm a painful conditioning stimulus (CS) may inhibit the perceived pain of a second painful stimulus (test stimulus). In recent years, CPM has been used to improve pain assessment of quantitative sensory testing for making better diagnosis and clinical decision. The aim of study is to provide a reliable CPM paradigm using thermal stimuli and to collect normative data from healthy subjects. Thirty-one healthy subjects are included. Each subject performed a baseline cold and warm thermal thresholds determination. The Medoc webinar CPM system has been used for the CPM session. The CS was a tonic heat pain (NRS > 5). Two thermodes, one used as painful stimulus, the other as CS, were applied in the same limb (forearm and leg) and in contralateral limbs. The test was repeated within 15 days. We found significant heat pain thresholds increase in all subjects (ipsilateral forearm: 8.4%, leg 6.6%; contralateral forearm 5.2%, leg 5.5%). No significant differences have been observed between the test and retest (p > 0.6), with good reliability (ICC 0.72). This CPM paradigm may be applied as a reliable test for diagnostic purpose.

Pain sensitivity profiles in patients with advanced knee osteoarthritis.

The development of patient profiles to subgroup individuals on a variety of variables has gained attention as a potential means to better inform clinical decision making. Patterns of pain sensitivity response specific to quantitative sensory testing (QST) modality have been demonstrated in healthy subjects. It has not been determined whether these patterns persist in a knee osteoarthritis population. In a sample of 218 participants, 19 QST measures along with pain, psychological factors, self-reported function, and quality of life were assessed before total knee arthroplasty. Component analysis was used to identify commonalities across the 19 QST assessments to produce standardized pain sensitivity factors. Cluster analysis then grouped individuals who exhibited similar patterns of standardized pain sensitivity component scores. The QST resulted in 4 pain sensitivity components: heat, punctate, temporal summation, and pressure. Cluster analysis resulted in 5 pain sensitivity profiles: a "low pressure pain" group, an "average pain" group, and 3 "high pain" sensitivity groups who were sensitive to different modalities (punctate, heat, and temporal summation). Pain and function differed between pain sensitivity profiles, along with sex distribution; however, no differences in osteoarthritis grade, medication use, or psychological traits were found. Residualizing QST data by age and sex resulted in similar components and pain sensitivity profiles. Furthermore, these profiles are surprisingly similar to those reported in healthy populations, which suggests that individual differences in pain sensitivity are a robust finding even in an older population with significant disease.

Quantitative sensory testing using DFNS protocol in Europe: an evaluation of heterogeneity across multiple centers in patients with peripheral neuropathic pain and healthy subjects.

Quantitative sensory testing (QST) in accordance with the DFNS (German Research Network on Neuropathic Pain) protocol assesses the function of afferent nerve fibers on the basis of 13 parameters. Within the consortia IMI (Innovative Medicines Initiative) Europain and Neuropain, QST results from pain research units experienced in QST across Europe can be compared for the first time. Aim of this analysis was to identify possible biases in the QST assessment between 10 centers from 8 different European countries. In total, 188 healthy subjects, 217 patients with painful polyneuropathy, and 150 patients with painful peripheral nerve injury were included in the analysis. Mixed effects models were constructed for each of the 11 normally distributed QST parameters with z-value as the dependent variable, and center as the random effect. The I statistic for heterogeneity was calculated, an index ranging from 0% (no heterogeneity) to 100% (perfect heterogeneity). Data from healthy subjects were comparable with the existing reference data base. Patients with polyneuropathy mainly displayed loss of sensory function, whereas patients with peripheral nerve injury often showed sensory loss combined with mechanical hyperalgesia. Heterogeneity was overall low between different centers and parameters. There was no systematic heterogeneity for patients with painful peripheral nerve injury and painful polyneuropathy. For healthy subjects, only blunt pressure pain threshold showed a considerable heterogeneity of 42% (95% confidence interval: 0%-66%). In conclusion, QST of both healthy subjects and patients with peripheral neuropathic pain is largely homogenous within the European centers, an essential prerequisite for performing multicenter QST-based studies.

Quantitative sensory testing of temperature, pain, and touch in adults with Down syndrome

The spinothalamic pathway mediates sensations of temperature, pain, and touch. These functions seem impaired in children with Down syndrome (DS), but have not been extensively examined in adults. The objective of the present study was to compare the spinothalamic-mediated sensory functions between adults with DS and adults from the general population and to examine in the DS group the relationship between the sensory functions and level of intellectual functioning. Quantitative sensory testing (QST) was performed in 188 adults with DS (mean age 37.5 years) and 142 age-matched control participants (median age 40.5 years). Temperature, pain, and touch were evaluated with tests for cold–warm discrimination, sharp–dull discrimination (pinprick), and tactile threshold, respectively. Level of intellectual functioning was estimated with the Social Functioning Scale for Intellectual Disability (intellectual disability level) and the Wechsler Preschool and Primary Scale of Intelligence – Revised (intelligence level). Overall, the difference in spinothalamic-mediated sensory functions between the DS and control groups was not statistically significant. However, DS participants with a lower intelligence level had a statistically significant lower performance on the sharp–dull discrimination test than DS participants with higher intelligence level (adjusted p=.006) and control participants (adjusted p=.017). It was concluded that intellectual functioning level is an important factor to take into account for the assessment of spinothalamic-mediated sensory functioning in adults with DS: a lower level could coincide with impaired sensory functioning, but could also hamper QST assessment.