Quantitative Sensory Testing Modalities Research Articles

Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK

ObjectiveThe chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS...

Quantitative sensory testing for assessment of somatosensory function in children and adolescents: a scoping review.

Quantitative sensory testing (QST) refers to a group of noninvasive psychophysical tests that examine responses to a range of calibrated mechanical and thermal stimuli. Quantitative sensory testing has been used extensively in adult pain research and has more recently been applied to pediatric pain research. The aims of this scoping review were to map the current state of the field, to identify gaps in the literature, and to inform directions for future research. Comprehensive searches were run in 5 databases. Titles, abstracts, and full texts were screened by 2 reviewers. Data related to the study aims were extracted and analyzed descriptively. A total of 16,894 unique studies were identified, of which 505 were screened for eligibility. After a full-text review, 301 studies were retained for analysis. Date of publication ranged from 1966 to 2023. However, the majority of studies (61%) were published within the last decade. Studies included participants across the developmental trajectory (ie, early childhood to adolescence) and most often included a combination of school-age children and adolescents (49%). Approximately 23% of studies were conducted in healthy samples. Most studies (71%) used only one QST modality. Only 14% of studies reported using a standardized QST protocol. Quantitative sensory testing in pediatric populations is an emerging and rapidly growing area of pain research. Future work is needed using comprehensive, standardized QST protocols to harness the full potential that this procedure can offer to our understanding of pediatric pain.

P111 Reliability of quantitative sensory testing, disease activity score 28, ultrasound and central aspects of pain questionnaire in individuals with rheumatoid arthritis

Abstract Background/Aims Disease Activity Score 28 (DAS28), ultrasound, quantitative sensory testing (QST) and central aspect of pain (CAP) questionnaire measure disease activity and pain hypersensitivity. We investigated their inter-rater and test-retest reliability in Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) participants. Methods Participants who attended the CAP-RA study visit and agreed to one or more reliability assessments were included. The same two raters completed all assessments, including clinical examination for DAS28, using a single blood sample per participant. QST modalities in the sequence: Pressure Pain detection Threshold (PPT) at the medial joint line of the most painful knee, tibialis anterior and contralateral brachioradialis, Temporal Summation (TS) at rectus femoris of the most painful knee and Conditioned Pain Modulation (CPM), with ischaemic arm pain conditioning and PPT at tibialis anterior. Ultrasound followed the Backhaus 7 protocol, plus the knee. Two trained sonographers scored each joint scan for grey scale (GS), power Doppler and a combined score (PDUS) using EULAR-OMERACT methodology. Joint scores were summated to give an overall score for GS, Doppler and PDUS. Participants could complete questionnaires at invitation, prior to and at baseline, 1-week post-baseline, prior to and at follow-up visit. Any combination of questionnaires completed within 7 days of each other assessed repeatability. Data were assessed for normality, interclass correlation coefficients, and Bland and Altman plots in R studio. Results 196 people were recruited into CAP-RA (median (IQR)) age 66 (58-75) y, 139 (75%) female, 190 (98%) white. 97 (49%) undertook study visits. Characteristics of the 66 people undertaking reliability did not significantly differ from the total population. Measurements are shown in Table 1. Moderate to excellent reliability was found across all measures except CPM (Table 1). The swollen joint count was the least reliable of the DAS28 components. Conclusion Measures of inflammatory disease activity and pain sensitivity are at least moderately reliable within a research context. Only low reliability for CPM might indicate imprecision, or reflect fluctuations in symptoms or pain sensitivity. High reliability of DAS28 and US might reflect relative stability of clinical signs of inflammation. Suppressing day-to-day fluctuations could reduce the unpredictability of rheumatoid arthritis. Disclosure S.L. Smith: None. V. Georgopoulos: None. O. Ifesemen: None. E. Ferguson: None. R.J. Wakefield: None. D. Wilson: None. P. Buckley: None. D. Platts: None. S. Ledbury: None. D.F. McWilliams: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB. D.A. Walsh: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB.

The interrater and test-retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis.

Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions. We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability. The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups. High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP. PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Classification of Qualitative Fieldnotes Collected During Quantitative Sensory Testing: A Step Towards the Development of a New Mixed Methods Approach in Pain Research.

PurposeQuantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach.Patients and MethodsQST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words.ResultsQualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes.ConclusionOur findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research.

Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study

BackgroundPain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA.Methods/designThis is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated.DiscussionThis study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation.Trial registrationClinicaltrials.gov NCT04515589. Date of registration 17 August 2020.

Examining somatosensory function by age, testing site, and modality

The purpose of this study was to systematically examine somatosensory function by age and testing site across a variety of quantitative sensory testing (QST) modalities and determine if age differences were associated with brain gray matter volume and cortical thickness. Healthy younger (n=22; mean (SD) age = 21.31 (1.54) years) and older adults (n=62; mean (SD) age= 72.11 (6.69) years) were recruited as part of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study. Participants underwent mechanical and thermal detection as well as pain perception applied to two different anatomical sites (metatarsal and thenar). MRI data was collected on a 3-Tesla scanner with a 32-channel radiofrequency coil. A repeated measures ANOVA examined differences in QST by age and test site. Freesurfer examined associations between QST modalities and brain structure in older adults. Significant test site by age interaction effects were observed for warm detection threshold (p=0.018, partial eta2=0.10) and heat pain threshold (p=0.014, partial eta2=0.12). Main effects of age were observed for mechanical detection threshold, vibratory detection threshold, cold detection threshold, warm detection threshold, heat pain threshold, heat pain rating (p's

Dietary Cholesterol is Associated with Increased Pain Sensitivity in Individuals with Chronic Low Back Pain

Chronic low back pain (cLBP) is one of the leading causes of pain and disability in adults in the United States. Given that approximately 90% of cLBP cases are of unknown pathogenic cause, it is imperative that other avenues to its onset be explored. Recently, it has been reported that diet quality can influence pain state via diet-induced inflammation and oxidative stress.The objective of this study was to assess the preliminary relationships between various nutrients and outcomes assessed in Quantitative Sensory Testing (QST) in individuals with cLBP. Eighty individuals with cLBP were recruited as a part of an on-going study. A diet recall was delivered to assess food intake 24 hours prior to pain testing and used to calculate a nutrient profile for each individual. Self-reported QST pain measures were obtained. Correlation analyses were used to examine the relationships between these variables. Significant positive correlations were found with multiple nutrients, but interestingly, dietary cholesterol in multiple QST modalities. Dietary cholesterol was significantly correlated with pain scores in cLBP participants during the cold pressor task (r=0.245, p=0.025), and pin prick temporal summation delta change scores at 256 nm size (r=0.235, p=0.030), and 512 nm size (r=0.272, p=0.012). Dietary cholesterol was significantly correlated with pain scores in cLBP participants in multiple modalities, indicating potential effects at multiple nociceptive fibers. It is possible that excess cholesterol peroxidation may be influencing inflammation and subsequent increases in pain sensitivity via oxidative stress in this population. Racial and Socioeconomic Differences in Chronic Low Back Pain

Sensory and pain modulation profiles of ongoing central neuropathic extremity pain in multiple sclerosis.

Central neuropathic extremity pain (CNEP) is the most frequent type of pain in multiple sclerosis (MS). The aim of the present study was to evaluate sensory and pain modulation profiles in MS patients with CNEP. In a single-centre observational study, a group of 56 CNEP MS patients was compared with 63 pain-free MS patients and with a sex- and age-adjusted control group. Standardized quantitative sensory testing (QST) and dynamic QST (dQST) protocols comprising temporal summation and conditioned pain modulation tests were used to compare sensory profiles. Loss-type QST abnormalities in both thermal and mechanical QST modalities prevailed in both MS subgroups and correlated significantly with higher degree of disability expressed as Expanded Disability Status Scale (EDSS). Comparison of sensory phenotypes disclosed a higher frequency of the 'sensory loss' prototypic sensory phenotype in the CNEP subgroup (30%) compared with pain-free MS patients (6%; p=.003). The role of aging process and higher lesion load in the spinothalamocortical pathway might be possible explanation for pain development in this particular 'deafferentation' subtype of central neuropathic pain in MS. We were unable to support the role of central sensitization or endogenous facilitatory and inhibitory mechanisms in the development of CNEP in MS. This article presents higher prevalence of the 'sensory loss' prototypic sensory phenotype in multiple sclerosis patients with central extremity neuropathic pain compared to pain-free patients. Higher degree of disability underlines the possible role of higher lesion load in the somatosensory pathways in this particular 'deafferentation' type of central neuropathic pain.

The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.

The use of quantitative sensory testing in cancer pain assessment: A systematic review.

To summarize the literature on the use of quantitative sensory testing (QST) in the assessment of pain in people with cancer and to describe which QST parameters consistently demonstrate abnormal sensory processing in patients with cancer pain. Medline, EMBASE, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain. Search strategies were based on the terms "quantitative sensory testing", "cancer", "pain", "cancer pain" and "assessment". Databases were searched from inception to January 2019. Data were extracted and synthesized narratively, structured around the different QST modalities and sub-grouped by cancer pain aetiology (tumour- or treatment-related pain). Searches identified 286 records of which 18 met the eligibility criteria for inclusion. Three studies included patients with tumour-related pain, and 15 studies included patients with pain from chemotherapy-induced peripheral neuropathy (CIPN). Across all studies, 50% (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44% (8/18) reported abnormal mechanical detection thresholds using von-Frey filaments and 39% (7/18) found abnormal pinprick thresholds. Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in a third of included studies. This systematic review highlights the lack of published data characterizing the sensory phenotype of tumour-related cancer pain. This has implications for our understanding of the underlying pathophysiological mechanisms of cancer pain. Understanding the multiple mechanisms driving cancer pain will help to move towards rational individualized analgesic treatment choices. This systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli. However, these findings are based primarily on studies of chemotherapy-induced peripheral neuropathy and data on tumour-related pain are lacking, warranting further research.

Local and Systemic Analgesic Effects of Nerve-Specific Acupuncture in Healthy Adults, Measured by Quantitative Sensory Testing.

This study aims to assess whether acupuncture analgesia's effects are local or systemic and whether there is a dose response for these effects. Twenty-eight healthy volunteers aged 18-45 were randomized to two doses of acupuncture using points closely associated with peripheral nerves in the legs. The lower-dose group involved acupoints overlying the deep peroneal nerve (DP), and the higher-dose involved acupoints overlying the deep peroneal and posterior tibial nerves (DPTN). Baseline and acupuncture quantitative sensory testing (QST) assessments were obtained locally in the calf and great toe and systemically in the hand. Results were analyzed using factorial repeated-measures analysis of variance for each of the QST variables-cold detection threshold (CDT), vibration detection threshold (VDT), heat pain threshold (HP0.5), and heat pain perception of 5/10 (HP5.0). Location (leg/hand) and time (baseline/acupuncture) were within-subject factors. Intervention (DP/DPTN) was a between-subject factor. CDT was increased in the calf (P < 0.001) and in the hand (P < 0.001). VDT was increased in the toe (P < 0.001) but not in the hand. HP0.5 was increased in the calf (P < 0.001) and in the hand (P < 0.001). HP5.0 was increased in the calf (P = 0.002) and in the hand (P < 0.001), with the local effect being significantly greater than the systemic (P = 0.004). In all of the above QST modalities, there was no difference between the low-dose (DP) and high-dose (DPTN) acupuncture groups. Acupuncture caused comparable local and systemic analgesic effects in cold detection and heat pain perception and only local effects in vibration perception. There was no clear acupuncture dose response to these effects.

Association between quantitative sensory testing and pain or disability in paediatric chronic pain: protocol for a systematic review and meta-analysis

IntroductionThis protocol describes the objective and methods of a systematic review of the association between quantitative sensory testing (QST) measures and pain intensity or disability in paediatric chronic pain (PCP)....

(327) Exactly What You Think: Perceived Threat and Challenge Predict Quantitative Sensory Testing Outcomes in Temporomandibular Joint Disorder

While perceived threat (anticipated harm) and challenge (test of abilities) have been previously found to predict pain intensity ratings to thermal stimuli in healthy populations, few studies have assessed the relationship between threat and challenge and experimental pain outcomes in patients with chronic pain. This study examined associations of perceived threat and challenge on quantitative sensory testing (QST) outcomes in patients with temporomandibular joint disorder (TMJD) and healthy controls. In the present study, 40 adults with TMJD (n = 35 female, mean age = 30.4, SD = 6.19) and 22 healthy controls (n = 18 female, mean age = 27.8, SD = 7.07) provided separate ratings of threat and challenge immediately prior to completing painful heat, pressure, and punctate QST. Participants provided ratings of pain intensity following each stimulus. In both patients with TMJD and healthy controls, challenge ratings correlated with ratings of thermal pain intensity (r= .30, p = .02), while ratings of both challenge and threat correlated with ratings of pressure and punctate pain intensity (r’s = .36 - .50, p’s .05). These results replicate and extend prior research by demonstrating that perceived threat and challenge of a QST procedure can predict pain outcomes in patients with chronic pain. Future research should explore relationships between perceptions of threat and challenge with other QST modalities (i.e., delayed-onset muscle pain, electric pain), and explore how perception of QST parameters may influence pain chronicity. Supported by NIDCRR00DE022368-03.

Reliability of pressure pain, vibration detection, and tactile detection threshold measurements in lower extremities in subjects with knee osteoarthritis and healthy controls

Objectives: Quantitative sensory testing (QST) is a method to assess somatosensory function in osteoarthritis (OA), but reliability data on the performance of different QST modalities on different joint structures are missing. The main aims of our study were to assess intertester and intratester reliability of tactile detection thresholds (TDTs), vibration detection thresholds (VDTs), and pressure pain thresholds (PPTs) on different knee joint structures.Method: In total, 32 subjects with knee OA and 32 volunteers with healthy knees participated. TDTs, VDTs, and PPTs were examined on the medial tibial condyle, medial tibiofemoral joint line, and rectus femoris muscle twice on the first visit and once after 1–3 weeks.Results: The intratester and intertester intraclass correlation coefficients (ICCs) of PPT measurements varied from 0.60 to 0.90 on different joint structures, showing good to excellent reliability. Intratester reliability (ICC 0.64–0.76) of VDT measurements was higher than intertester reliability (0.48–0.75). The intertester reliability of TDT measurements was excellent in subjects with knee OA (ICC 0.84–0.86) and good in controls (0.67) on the medial tibial condyle. Intratester reliability of TDT measurements varied greatly.Conclusion: PPT testing is a reliable tool for measuring pain thresholds on different joint structures. The VDT measurement is reliable when taken by the same evaluator. The reliability of TDT measurements depends on the site of the measurement.

Quantitative sensory testing in patients with migraine: a systematic review and meta-analysis.

Quantitative sensory testing (QST) is widely used to assess somatosensory function by application of controlled stimuli across a variety of modalities. The aim of the present meta-analysis is to synthesize QST results across a wide array of studies of patients with migraine to identify the QST parameters that are reliably different between patients with migraine and healthy controls. In addition, we aimed to determine whether such differences vary according to stimulus location. A comprehensive literature search (up to January 2017) was conducted, which included studies comparing QST parameters between patients with migraine and healthy controls. For each QST modality, we calculated up to 3 meta-analyses for combined (combined data from multiple testing locations), local (head and neck), and nonlocal (outside the head or neck) locations. A total of 65 studies were included in the meta-analyses. Lower heat and pressure pain thresholds were observed in patients with migraine compared with healthy controls in the combined locations. Importantly, lower pressure pain threshold in patients with migraine was found in local areas but not in nonlocal areas. In addition, patients with migraine had higher pain ratings to cold suprathreshold stimuli for combined and nonlocal areas, and higher pain ratings to electrical suprathreshold stimuli for nonlocal areas. This meta-analysis indicates that the alterations in nociceptive processing of patients with migraine may be modality, measure, and location specific. These results provide researchers and clinicians the evidence to choose QST parameters optimally suited for differentiating patients with migraine and healthy controls.

Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis.

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition.

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an α-galactosidase A enzyme deficiency due to pathogenic variants in the α-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite diagnosis of FD has important consequences for treatment and counselling. We assessed the diagnostic value of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) for patients with an uncertain FD diagnosis. All patients with a GLA variant who initially presented at the Academic Medical Center with an uncertain FD diagnosis were included. A biopsy of an affected organ in a patient or family member showing FD characteristic storage is used as a reference standard for a diagnosis of FD. All patients underwent a comprehensive QST protocol and IENFD assessment which was compared to age and gender-matched healthy controls. Sensitivity and specificity were calculated for a combination of ≥1 abnormal QST modality and an abnormal IENFD. Twenty-six patients participated (nonclassical FD n = 18, 9 males; no FD n = 5, 3 males; uncertain n = 3, 1 male). Of the patients classified as nonclassical FD, 28% had ≥1 abnormal QST modalities, and 83% had an abnormal IENFD. From the patients without FD, 20% had ≥1 abnormal QST modality, and IENFD was abnormal in 25% (1 not available). Sensitivity was 28% and specificity 80%. In our study cohort, QST and IENFD could not reliably distinguish patients with FD from those without FD.

A pain model with a neuropathic somatosensory lesion: Morton neuroma

A randomized, double-blind, three-period cross-over study was performed to characterize the sensory phenotype and pain demographics in patients with Morton neuroma (n=27) and to explore the effects of local administration (2mL) of placebo and lidocaine (1 and 10mg/mL) around the neuroma. Using the pain quality assessment scale (PQAS), the highest rating was seen for unpleasant pain and intensity of deep pain and the lowest for sensitive skin. Ongoing pain was reported in 32% of patients. Patients reported mild to moderate average pain, and that pain had interfered with sleep only marginally. Quantitative sensory testing (QST) measurements in the innervation territory showed hypophenomena or hyperphenomena in all patients, indicating that all had neuropathy. There was no particular QST modality that appeared to be specifically affected. Even the high-dose lidocaine resulted in limited effects on nerve-impulse conduction as judged by the effect on QST variables. However, both doses of lidocaine significantly reduced pain after step-ups, compared to placebo, indicating that lidocaine in this setting affected predominantly impulse generation and not impulse conduction. Following placebo treatment, pain after step-ups was similar in patients with and without hyperalgesia, indicating that the presence of hyperalgesia does not affect the pain intensity evoked by step-ups or walking.This pain model in patients with Morton neuroma allows investigation of drugs in a cross-over design and provides an opportunity to explore drug effects on both pain and QST variables. Commonly, neuromas are surgically removed and can be characterized in depth in vitro, thereby allowing close links to be established between pathophysiology and drug effect.