The Contribution of Baseline Circulating Endocannabinoids to Individual Differences in Human Pain Sensitivity: A Quantitative Sensory Testing Study

Quantitative sensory testing: identifying pain characteristics in patients with osteoarthritis

BackgroundWhether patient’s experience of fibromyalgia severity is related to measures of pain sensitisation assessed by quantitative sensory testing is not clear. How disease duration effects the relationship between disease severity...

Pain sensitization in knee osteoarthritis (OA) is associated with greater symptom severity and poorer clinical outcomes. Measures that identify pain sensitization and are accessible to use in clinical practice have been suggested to enable more targeted treatments. This merits further investigation. This study examines the relationship between quantitative sensory testing (QST) and clinical measures of pain sensitization in people with knee OA. A secondary analysis of data from 134 participants with knee OA was performed. Clinical measures included: manual tender point count (MTPC), the Central Sensitization Inventory (CSI) to capture centrally mediated comorbidities, number of painful sites on a body chart, and neuropathic pain-like symptoms assessed using the modified PainDetect Questionnaire. Relationships between clinical measures and QST measures of pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation were investigated using correlation and multivariable regression analyses. Fair to moderate correlations, ranging from -0.331 to -0.577 (P<0.05), were identified between MTPC, the CSI, number of painful sites, and PPTs. Fair correlations, ranging from 0.28 to 0.30 (P<0.01), were identified between MTPC, the CSI, number of painful sites, and conditioned pain modulation. Correlations between the clinical and self-reported measures and temporal summation were weak and inconsistent (0.09 to 0.25). In adjusted regression models, MTPC was the only clinical measure consistently associated with QST and accounted for 11% to 12% of the variance in PPTs. MTPC demonstrated the strongest associations with QST measures and may be the most promising proxy measure to detect pain sensitization clinically.

Abnormalities in pain regulatory mechanisms are common in patients with rheumatoid arthritis (RA). We investigated whether pain sensitization changes after treatment with a disease-modifying antirheumatic drug (DMARD) and explored associations between changes in pain sensitization and disease activity. We included 182 participants with active RA initiating/switching DMARD therapy who were observed for 12 weeks. To assess pain sensitization, participants underwent quantitative sensory testing (QST), including pressure pain thresholds (PPTs) at multiple anatomic sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). RA disease activity was measured using the Disease Activity Score 28 with C-reactive protein (DAS28-CRP) and its components. Mean changes in QST measures were examined from baseline to 12 weeks, and associations between QST and disease activity measures were explored using Pearson correlation coefficients and adjusted linear regression analyses. PPTs significantly increased (improved) at multiple anatomic sites following 12 weeks of DMARD therapy. No significant changes were observed in TS or CPM. Increased PPTs at multiple anatomic sites were associated with reductions in DAS28-CRP, swollen joint count, tender joint count, and improvements in patient global assessment. No significant associations were observed between TS, CPM, and disease activity. Pain sensitivity improved after 12 weeks of DMARD therapy. These improvements were associated with reductions in disease activity.

Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA. Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures. Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT (r range = -0.31 to -0.21), and TS (r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components. FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization.

BackgroundPeople with osteoarthritis (OA) can experience both nociceptive pain, as a result of local joint damage, and pain that is indicative of abnormal central pain processing. Quantitative sensory testing (QST)...

<h3>Background</h3> People with osteoarthritis (OA) can experience both nociceptive pain, as a result of local joint damage, and pain that is indicative of abnormal central pain processing. Quantitative sensory testing (QST) is psychophysical testing of somatosensory function and can been used to investigate somatosensory abnormalities in people with OA. <h3>Objectives</h3> The aim of this study was to assess the reliability discriminant ability of two different mechanical stimuli for QST measurements, pressure and punctate, in people with knee OA and healthy participants. <h3>Methods</h3> Twenty six knee OA participants and 25 healthy participants were recruited. QST was performed in all participants at three sites on the body (sternum, index knee and anterior tibia). Two mechanical QST modalities (pressure and punctate) were performed. Pressure pain threshold (PPT) was assessed using digital algometry. Punctate QST measurements, {mechanical pain threshold (MPT), mechanical pain sensitivity (MPS) and wind-up ratio (WUR)}, were assessed using pinprick stimulators. The procedures were repeated during a second assessment four weeks later by the same examiner to determine repeatability. All participants completed the Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire (Rasch transformed). <h3>Results</h3> The mean age for OA participants was 66 years (standard deviation (SD) (9), (50% female) and for the healthy participants was 58 years (SD 11), (48% female). People with knee OA demonstrated significantly higher values on ICOAP Rasch transformed; Intermittent {mean 7.13 (4.47) and Constant mean 4.40 (4.47)} than healthy participants; Intermittent {mean 1.12 (2.31) and Constant {mean 0.29 (1.03)} (<i>P</i>&lt;0.001). The test-retest reliability of the QST measurements before and after 4 weeks interval expressed as intraclass correlation coefficients (ICCs) are given in Table 1. People with knee OA had significantly lower PPT at knee and tibia than normal controls (Graph). Differences between OA and control groups remained significant after adjustment for age and sex. Whereas there were no significant differences found in any punctate QST measurements between knee OA and healthy participants. <h3>Conclusions</h3> This study demonstrated that PPT is a reliable QST measurement with less variability compared to other mechanical QST measurements assessed. PPT at the tibia, a site distal to the affected joint, is believed to reflect augmented central pain processing. PPT may be a preferred QST modality to investigate altered central pain processing in people with OA. <h3>References</h3> R. Rolke et al. Pain 123 (2006), 231 – 243. A.K. Suokas et al. Osteoarthritis Cartilage 10 (2012), 1075–1085 V. Wylde et al. Osteoarthritis Cartilage 19 (2011), 655–658 M Pigg et al. Pain 148 (2010), 220 – 226. <h3>Disclosure of Interest</h3> None declared

BackgroundThis study described a sensory profile of participants with chronic pain (CP) in a previously reported feasibility RCT, in terms of quantitative sensory testing (QST) measures and the Central Sensitisation Inventory (CSI).AimsThe study aimed to explore the changes in QST measures and the CSI in this sample following participation in a mindfulness and physical activity intervention compared to an online self-management guide.MethodsParticipants were randomised into (i) a combined mindfulness and exercise online interactive group or (ii) an online self-management group. Pressure pain thresholds (PPT), temporal summation (TS), conditioned pain modulation (CPM) measures, and the CSI were completed with participants at baseline and post-intervention.ResultsBaseline (n = 33) and post-intervention (n = 22) measurements were completed. High mean CSI scores (54.69, SD 23.85) were noted at baseline in participants, indicating the presence of central sensitisation [n = 33; 70% (n = 23) score > 40]. Mean baseline scores for TS were high (2.64, SD 1.60), indicating the presence of pain facilitation, and variable results were observed for baseline PPT and CPM measures. The combined intervention was not found to be superior to a self-management guide in this cohort in terms of changes in PPT, TS, and CPM measures and the CSI.ConclusionsHigh baseline CSI and TS scores were identified in the cohort at baseline, with no notable trends identifiable with regard to changes in QST scores or the CSI post-intervention. Further studies are recommended with larger sample sizes in order to understand changes in QST measures following participation in interventions of this nature.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11845-025-03947-y.

Background In patients with idiopathic intracranial hypertension (IIH) headache often persist as a disabling symptom even after intracranial pressure (ICP) has normalized. Yet very little is known about the mechanisms of chronification. Aim To explore pain perception in patients with IIH in a controlled design at time of diagnosis and after 3 months of treatment. Materials and methods We explored pain perception in patients with newly diagnosed IIH by Quantitative Sensory Testing (QST) measuring cephalic and extra-cephalic supra-threshold pain ratings and pain thresholds for pressure and electrical stimulation. QST was performed at diagnosis and after one and three months. ICP was measured at baseline and at the 3-month follow-up. QST measurements from sex-matched controls were used for comparisons. Headache was assessed by monthly standardized interviews and headache diaries. Results At baseline IIH patients (n = 28) showed no consistent abnormalities in pain sensitivity or thresholds (p > 0.09 for all comparisons to healthy controls (n = 28). Although headache improved markedly and ICP normalized in 52%, there was no consistent change in pain sensitivity from baseline to follow-up (p > 0.09 for all variables). Patients with (54%) and without persistent chronic headache (46%) 3 months after diagnosis showed no different pain perception either at baseline or at the 3-month follow-up. Conclusions Although headache persisted as a chronic symptom in half of the patients we found no evidence of increased central pain sensitivity suggesting that headache chronification in IIH is caused by mechanisms other than central sensitization.

BackgroundOsteoarthritis (OA) is a major cause of chronic pain; however, the exact pathophysiology of OA pain remains poorly understood. Quantitative sensory testing (QST) is a tool used to assess pain...

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

This meta-analysis aimed to evaluate quantitative sensory testing (QST) evidence for pain processing in patients with the muscle pain subtype of temporomandibular disorders (mTMD). A comprehensive systematic electronic search strategy was performed in online literature databases. All full-text observational studies published up to July 2021 with the aim of investigating pain sensitization in humans with mTMD using QST measures were eligible for inclusion. Meta-analysis of QST data was performed using a random effects model, which included results comparing patients with mTMD to healthy controls, and standard mean difference (SMD) results were analyzed. Twelve studies with 732 participants (371 patients with mTMD and 361 healthy controls) were analyzed following screening and quality appraisal. Compared with healthy controls, patients with mTMD had significantly lower pressure pain threshold (SMD - 1.10, 95% confidence interval [CI] - 1.52 to - 0.68) with high heterogeneity (Tau2 = 0.61, I2 = 86%), and significantly lower mechanical pain threshold (SMD - 0.64, 95% CI - 0.95 to - 0.32) with no heterogeneity (Tau2 = 0.00, I2 = 0%). No difference was observed in the cold pain threshold (SMD 0.16, 95% CI - 0.13 to 0.45), heat pain threshold (SMD - 0.13, 95% CI - 0.40 to 0.15), and wind-up ratio (SMD 0.63, 95% CI - 0.11 to 1.38) between patients with mTMD and healthy controls. Other QST parameters were also discussed. The study results suggest that the pain processing of deep tissues is likely sensitized in mTMD and calls for more QST studies with standard procedures to reduce inter-study heterogeneity. The major findings of this meta-analysis support using PPT to examine the pain processing in patients with mTMD in clinical scenario.

Quantitative Sensory Testing in Children with Sickle Cell Disease

BackgroundWhile acupuncture’s mechanism of action is not fully understood, there is consensus that the nervous system plays a key role in processing its effects. This research is based on the structural theory of acupuncture, which aims to correlate the location of acupuncture points to peripheral nerves, spinal segments, and spinal plexuses. This mechanistic study explores the close anatomical association between the Pericardium meridian/median nerve and the Heart meridian/ulnar nerve in an attempt to produce electrophysiologic data measuring acupuncture’s direct, nerve-specific effect on the underlying nerves. Specifically, the purpose of this research is to use nerve conduction studies (NCSs) and quantitative sensory testing (QST) to assess for any local, nerve-specific effect of three acupuncture modalities on two anatomically distinct nerves in the forearm — the median and ulnar nerves — in subjects with carpal tunnel syndrome (CTS). The choice of CTS as an injured nerve model allows for comparisons between the response in an injured nerve (median) to that of a healthy one (ulnar).MethodsSubjects with mild to moderate CTS will be randomized to three intervention groups: manual acupuncture and low- and high-frequency electroacupuncture. Each subject will receive two treatments, 1 week apart, to points in the forearm, which overlay the median nerve (Pericardium meridian) or the ulnar nerve (Heart meridian). Acupuncture will be administered in random order to minimize learning effects in sensory testing. During Week 1, baseline NCS and QST (vibration and cold detection thresholds) will be obtained in both nerve territories, followed by acupuncture and post-acupuncture NCS and QST measurements in both nerve territories. During Week 2, repeat baseline QST and NCS measurements will be obtained, followed by acupuncture to points overlying the nerve not treated in Week 1, followed by post-acupuncture NCS and QST measurements in both nerve distributions.DiscussionThis works aims to capture and characterize the local effects of acupuncture on an underlying nerve and compare them to those on a neighboring nerve. Quantifying acupuncture’s effects using physiologic parameters and discrete values could standardize treatment regimens and help assess their therapeutic effect.Trial registrationClinicalTrials.gov, NCT03036657. Registered on 30 January 2017. Retrospectively registered.

e21595 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a complex, dose-limiting toxicity impacting prognosis and quality of life. The optimal approach to identification and assessment remains unclear. This study aims to prospectively characterize the development and trajectory of CIPN using a combination of patient-reported outcomes (PROs) and objective Quantitative Sensory Testing (QST) measures in gynaecological, colorectal and lung cancer patients receiving neurotoxic platinum and/or taxane-based chemotherapy. Methods: Patients (n = 33, mean age 60.8) were evaluated at baseline prior to chemotherapy, during (every 3 weeks) and post-treatment every 3 months up to 1 year. Assessments at each time point included: PRO (EORTC QLQ-CIPN20 questionnaire) and QST measures (thermal and mechanical detection and grooved pegboard test). Statistical modelling using repeated measures analysis by patient was conducted. Results: Significant and parallel changes were observed in PROs and QST measures over time. Total EORTC score (sensory, motor and autonomic) increased in severity from baseline at all time points, peaking at 3 months post-treatment (34.8% increase; p &lt; 0.0001) and persisting at 1 year (17.9% increase; p = 0.01). Every increase by one point in EORTC sensory score over time corresponded with an elevation in QST parameters: warm detection threshold (upper limb; p = 0.02 and lower limb; p = 0.03) and mechanical detection threshold, MDT (upper limb; p = 0.04 and lower limb; p = 0.02). Equally, rising total EORTC and motor score were related to increasing MDT in the upper limb p = 0.02 and p = 0.003 respectively. A delay of one second taken to complete the grooved pegboard test (dominant hand) was linked to a proportional increase in EORTC motor score (p = 0.01). Conclusions: Associations are shown here amongst PROs and QST parameters providing an opportunity to quantify and synthesize objective with subjective measures of neuropathy in CIPN patients. This may have potentially informative implications to underlying mechanisms of CIPN symptom burden, contributing to a more comprehensive clinical picture and allow stratification of patients by phenotype severity. Additional studies are warranted.