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.

A randomized controlled trial on long-term effectiveness of a psychosocial aftercare program following paediatric chronic pain treatment: Who benefits the most?

BACKGROUND: For paediatric chronic pain patients, intensive interdisciplinary pain treatment (IIPT) is a well-established treatment. The treatment's short-term effectiveness can be improved by an additive psychosocial aftercare (PAC). However, neither the program's long-term effectiveness nor the patients in particular need have been investigated yet. METHODS: This study aimed at determining the long-term effects of PAC and detecting predictors of treatment outcome within a multicentre randomized controlled trial measured at five time points up to 12 months after discharge. At inpatient admission to IIPT, patients (N = 419, 14.3 years of age, 72.3% female) were randomly assigned to intervention or control group. After IIPT discharge, the intervention group received PAC, whereas the control group received treatment as usual (TAU). Patient-reported outcomes included pain and emotional characteristics. Clinicians assessed potential psychosocial risk factors and their prognosis of treatment outcome. Statistical analyses included mixed-models and univariable logistic regressions. RESULTS: Data at the 12-month follow-up (n = 288) showed a significant benefit of PAC compared with TAU; the majority (59.0%) of patients in the PAC-group reported no chronic pain compared to 29.2% of TAU-patients (p < 0.001). Patients with a single parent specifically benefited from PAC compared to TAU. Clinicians were able to make a reliable prognosis of treatment outcome, but did not successfully predict which patients would benefit the most from PAC. CONCLUSIONS: Study results suggest that PAC is highly effective irrespective of patient characteristics, but particularly for patients with single parents. Its broad implementation could help to improve the long-term outcomes of youth with severely disabling chronic pain. SIGNIFICANCE: A psychosocial aftercare following paediatric IIPT leads to significantly better pain and emotional outcomes compared to treatment as usual up to 12 months after discharge, especially for patients with single parents.

Exploring the Mechanisms Underlying the Effectiveness of Psychosocial Aftercare in Pediatric Chronic Pain Treatment: A Qualitative Approach.

A newly developed specialized psychosocial aftercare program (PAC) for pediatric patients with chronic pain following an intensive interdisciplinary pain treatment (IIPT) was found to be significantly more effective than IIPT alone. This qualitative study aimed to gain further insight into the mechanisms and prerequisites for the effectiveness of this specialized aftercare program. We conducted structured telephone interviews with patients, parents, and health care professionals conducting PAC. A total of 16 interviews were conducted-seven interviews with parents, six interviews with patients, and three interviews with health care professionals-and transcribed verbatim. Data were analyzed using reflexive thematic analysis. Four major themes consisting of 20 subcategories were identified, namely (1) frame conditions, (2) person factors, (3) stabilization and (4) catalyst. The foundations of treatment success are frame conditions, such as flexibility or constancy, and person factors, such as respect or expertise. Based on these foundations, stabilization is achieved through security, mediation, orientation and support. Altogether, these components of PAC reveal their potential as catalysts for further improvement even after discharge from IIPT. Overall, patients and their families emphasized widespread personal relevance and acceptance of the PAC program. The findings of this study may be employed in the development of other aftercare programs or interventions involving families in the context of psychotherapeutic and psychosocial health care.

Effectiveness of a Psychosocial Aftercare Program for Youth Aged 8 to 17 Years With Severe Chronic Pain: A Randomized Clinical Trial.

Importance: Severe chronic pediatric pain causes individual suffering and significantly affects social functioning and psychological well-being. For children with high pain severity, intensive interdisciplinary pain treatment (IIPT) is a well-established treatment. However, across specialized centers, it is not sufficient for all patients. Objective: To evaluate the effectiveness of a psychosocial aftercare (PAC) program for pediatric patients with severe chronic pain followed up for 6 months after discharge from IIPT. Design, Setting, and Participants: This multicenter randomized clinical trial with 4 assessment points (pre-IIPT, immediately post-IIPT, 3 months, and 6 months) was conducted at 3 pediatric specialized tertiary care pain centers in Germany between September 11, 2018, and March 31, 2020. Included patients were aged 8 to 17 with a severe chronic pain condition who had been admitted for IIPT. Data were analyzed from June 8 to September 4, 2020. Interventions: Patients and their families were randomly assigned to 1 of 2 study groups at inpatient IIPT admission. Both groups received standardized 3- to 4-week IIPT. After IIPT discharge, the intervention group received PAC and the control group received usual care. PAC involved ongoing contact with a social worker for as long as the family requested the support, up to a maximum of 6 months. Main Outcomes and Measures: The primary outcome measure was pain at 6 months, measured using the Chronic Pain Grading (CPG), an instrument based on an algorithm indicating severity of the chronic pain disorder. Secondary outcomes included other pain-related and emotional parameters. Results: A total of 419 patients were randomized (mean [SD] age, 14.3 [2.1] years; 303 [72.3%] girls; 116 [27.7%] boys), with 218 assigned to usual care and 201 assigned to PAC. At baseline in both groups, the median (IQR) CPG was 3 (2-4). Superiority of PAC compared with usual care was demonstrated at 6 months (median [IQR] CPG: usual care, 2 [2-3]; PAC, 1 [1-2]; r = 0.30; 95% CI, 0.17-0.41). Additionally, PAC significantly improved emotional parameters (eg, significant time × group interaction: b = -8.84; P < .001). Conclusions and relevance: This randomized clinical trial found that PAC improved pain-related and emotional parameters during the intervention 6 months after discharge from IIPT. Future research is needed to investigate the intervention's long-term effects. Trial Registration: German Clinical Trials Register ID: DRKS00015230.

Assessment of Sleep-Related Problems in Children with Cerebral Palsy Using the SNAKE Sleep Questionnaire.

Cerebral palsy (CP) represents the most common motor impairment in childhood. The presence of sleep problems has not yet been investigated with an instrument specifically designed for this population. In this hospital-based, prospective study, N = 100 children (M = 7.9, range: 2-18 years) with CP were included. All patients underwent pediatric neurologists' screening incorporating instruments (Data Collection Form; Gross Motor Functions Classification System, GMFCS; Bimanual Fine Motor Function, BFMF) recommended by the "Surveillance of Cerebral Palsy in Europe (SCPE)". Parents completed the "Sleep Questionnaire for Children with Severe Psychomotor Impairment (SNAKE)". Children's sleep behavior was increasingly conspicuous, with greater gross motor (SNAKE scales: disturbances remaining asleep, daytime sleepiness) and fine motor (additionally SNAKE scale arousal and breathing problems) functional impairment. Overall, a proportion of children showed sleep behavior outside the SNAKE's normal range. No relevant sleep differences were identified between different CP subtypes and comorbidities. Applying a population-specific questionnaire, children's functional impairment seems to be more relevant to their sleep behavior than the CP subtype or CP comorbidities.

Differential Diagnosis of Acquired and Hereditary Neuropathies in Children and Adolescents-Consensus-Based Practice Guidelines.

Disorders of the peripheral nerves can be caused by a broad spectrum of acquired or hereditary aetiologies. The objective of these practice guidelines is to provide the reader with information about the differential diagnostic workup for a target-oriented diagnosis. Following an initiative of the German-speaking Society of Neuropaediatrics, delegates from 10 German societies dedicated to neuroscience worked in close co-operation to write this guideline. Applying the Delphi methodology, the authors carried out a formal consensus process to develop practice recommendations. These covered the important diagnostic steps both for acquired neuropathies (traumatic, infectious, inflammatory) and the spectrum of hereditary Charcot-Marie-Tooth (CMT) diseases. Some of our most important recommendations are that: (i) The indication for further diagnostics must be based on the patient's history and clinical findings; (ii) Potential toxic neuropathy also has to be considered; (iii) For focal and regional neuropathies of unknown aetiology, nerve sonography and MRI should be performed; and (iv) For demyelinated hereditary neuropathy, genetic diagnostics should first address PMP22 gene deletion: once that has been excluded, massive parallel sequencing including an analysis of relevant CMT-genes should be performed. This article contains a short version of the guidelines. The full-length text (in German) can be found at the Website of the "Arbeitsgemeinschaft der Wissenschftlichen Medizinischen Fachgesellschaften e.V. (AWMF), Germany.

Clinical and Magnetic Resonance Imaging Outcome Predictors in Pediatric Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

OBJECTIVE: To evaluate disease symptoms, and clinical and magnetic resonance imaging (MRI) findings and to perform longitudinal volumetric MRI analyses in a European multicenter cohort of pediatric anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) patients. METHODS: We studied 38 children with NMDARE (median age = 12.9 years, range =1-18) and a total of 82 MRI scans for volumetric MRI analyses compared to matched healthy controls. Mixed-effect models and brain volume z scores were applied to estimate longitudinal brain volume development. Ordinal logistic regression and ordinal mixed models were used to predict disease outcome and severity. RESULTS: Initial MRI scans showed abnormal findings in 15 of 38 (39.5%) patients, mostly white matter T2/fluid-attenuated inversion recovery hyperintensities. Volumetric MRI analyses revealed reductions of whole brain and gray matter as well as hippocampal and basal ganglia volumes in NMDARE children. Longitudinal mixed-effect models and z score transformation showed failure of age-expected brain growth in patients. Importantly, patients with abnormal MRI findings at onset were more likely to have poor outcome (Pediatric Cerebral Performance Category score > 1, incidence rate ratio = 3.50, 95% confidence interval [CI] = 1.31-9.31, p = 0.012) compared to patients with normal MRI. Ordinal logistic regression models corrected for time from onset confirmed abnormal MRI at onset (odds ratio [OR] = 9.90, 95% CI = 2.51-17.28, p = 0.009), a presentation with sensorimotor deficits (OR = 13.71, 95% CI = 2.68-24.73, p = 0.015), and a treatment delay > 4 weeks (OR = 5.15, 95% CI = 0.47-9.82, p = 0.031) as independent predictors of poor clinical outcome. INTERPRETATION: Children with NMDARE exhibit significant brain volume loss and failure of age-expected brain growth. Abnormal MRI findings, a clinical presentation with sensorimotor deficits, and a treatment delay > 4 weeks are associated with worse clinical outcome. These characteristics represent promising prognostic biomarkers in pediatric NMDARE. ANN NEUROL 2020 ANN NEUROL 2020;88:148-159.

Long-term small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation.

PURPOSE: We aimed at describing for the first time peripheral small-fiber neurotoxicity and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation (SCT). METHODS: In a cross-sectional, retrospective, single-center study, we assessed 25 relapse-free long-term survivors (median age at SCT: 11 ± 4.9 years; median time between SCT and testing: 8.25 years, 19 males) using a reduced version of the pediatric-modified total neuropathy score for clinical assessment and Quantitative Sensory Testing (QST). INCLUSION CRITERIA: [Formula: see text] 6 years old at testing, [Formula: see text] 18 years old at time of SCT, [Formula: see text] 1 year between SCT and testing. RESULTS: Nine patients (36%) had peripheral neuropathy as defined by the clinical red-pmTNS (≥ 4). The QST parameters mechanical pain sensitivity, mechanical detection threshold, thermal sensory limen, vibration detection threshold and pressure pain threshold were significantly abnormal in the survivor cohort (p < 0.0038). Except for one, all survivors showed at least one abnormal QST parameter. When using QST, signs of small and large fiber dysfunction were present in 22 (88%) and 17 (68%) survivors, respectively. More than half of all survivors were found to experience pathologic sensitization to pain. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Survivors of pediatric acute lymphoblastic leukemia after SCT are at high risk for long-term peripheral neuropathy with a dominating small-fiber and pain sensitization pattern.

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

INTRODUCTION: This 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). The review will also assess whether the relationship strength is moderated by variables related to the QST method and pain condition; the use of QST in PCP (modalities, outcome measures and anatomical test sites as well as differentiating between pain mechanisms (eg, neuropathic vs nociceptive) and in selecting analgesics); the reliability of QST across the paediatric age range; the ability of QST to differentiate patients with chronic pain from healthy controls; and differences between anatomical test sites. METHODS AND ANALYSIS: Medline, PsycINFO, CINHAL, Web of Science, Scopus, Cochrane Library and OpenGrey will be searched. English language studies will be eligible if they recruit a sample aged 6-24 (inclusive) with chronic pain, including primary and secondary pain; apply at least one of the following QST modalities: chemical, electrical, mechanical (subgroups include pressure, punctate/brush and vibratory) or thermal stimulus to measure perception of noxious or innocuous stimuli applied to skin, muscle or joint; use a testing protocol to control for stimulus properties: modality, anatomical site, intensity, duration and sequence. Following title and abstract screening, the full texts of relevant records will be independently assessed by two reviewers. For eligible studies, one reviewer will extract study characteristics and data, and another will check for accuracy. Both will undertake independent quality assessments using the Appraisal Tool for Cross-Sectional Studies. A qualitative synthesis will be presented with discussion centred around different QST modalities. Where eligible data permit, meta-analyses will be performed separately for different QST modalities using comprehensive meta-analysis. ETHICS AND DISSEMINATION: Review findings will be reported in a peer-reviewed journal and presented at conferences. The study raises no ethical issues. PROSPERO REGISTRATION NUMBER: CRD42019134069.

Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure.

BACKGROUND: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. OBJECTIVE: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. METHODS: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. RESULTS: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. CONCLUSIONS: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

[Chronic Headache in Children and Adolescents]. / Chronische Kopfschmerzen bei Kindern und Jugendlichen.

Primary headache disorders such as migraine and tension-type headache begin as early as childhood or adolescence. Prevalence increases during primary school and adolescence. In tension-type headache, central pain sensitization and activation of central nociceptive neurons plays an important role. Migraine is a primary brain disorder with abnormalities in pain modulating systems and cortical stimulus processing. Bio-psycho-social factors play a decisive role in both types of headache. Secondary headaches due to an inflammatory or a structural brain alteration are rare. Diagnosis is based on clinical criteria. Typical recurrent headaches are diagnosed by patient's history and physical examination. In case of abnormalities, further diagnostic is needed. Treatment of tension-type headache is focused on multimodal pain therapy, treatment of migraine is focused on medication of attacks and secondary headaches need treatment of the underlying disease. Treatment goals are the reduction of pain perception, promotion of control and self-efficacy experiences, the increase of physical performance as well as the resumption of normal everyday structures and social contacts as a prerequisite for an increasing pain reduction.

The Unfavorable Alliance of Pain and Poor Sleep in Children with Life-Limiting Conditions and Severe Psychomotor Impairment.

A high prevalence of sleep problems exists in children and adolescents with life-limiting conditions (LLC) and severe psychomotor impairment (SPMI). This study aimed to compare the impacts of various child-related (pain, epilepsy, repositioning, medical care) and environment-related (light, noise, TV/radio, open door) factors on sleep in this vulnerable population. Data were obtained through the “Sleep Questionnaire for Children with Severe Psychomotor Impairment” (SNAKE) by proxy assessment. n = 212 children (mean age: 10.4 years) were included in the analyses. Logistic and linear regression models were used to compare child- and environment-related factors against the global rating of children’s sleep quality, five SNAKE scales, children’s sleep duration, and sleep efficacy. Pain increased the risk of sleeping poorly four-fold (OR (odds ratio) = 4.13; 95% CI (confidence interval): 1.87⁻9.13) and predicted four sleep problems as assessed by the SNAKE. Children who needed to reposition during the night were at three times greater risk of sleeping poorly (OR = 3.08; 95% CI: 1.42⁻6.69). Three of the five SNAKE scales were predicted through nocturnal repositioning. Repositioning and epilepsy predicted a reduced sleep duration and low sleep efficacy. None of the environment-related factors exhibited statistically significant results. This study emphasizes the urgent need for reliable pain detection in the context of sleep disturbances in severely ill children.

A Sleep Questionnaire for Children with Severe Psychomotor Impairment (SNAKE)-Concordance with a Global Rating of Sleep Quality.

Sleep problems are a common and serious issue in children with life-limiting conditions (LLCs) and severe psychomotor impairment (SPMI). The "Sleep Questionnaire for Children with Severe Psychomotor Impairment" (Schlaffragebogen für Kinder mit Neurologischen und Anderen Komplexen Erkrankungen, SNAKE) was developed for this unique patient group. In a proxy rating, the SNAKE assesses five different dimensions of sleep(-associated) problems (disturbances going to sleep, disturbances remaining asleep, arousal and breathing disorders, daytime sleepiness, and daytime behavior disorders). It has been tested with respect to construct validity and some aspects of criterion validity. The present study examined whether the five SNAKE scales are consistent with parents' or other caregivers' global ratings of a child's sleep quality. Data from a comprehensive dataset of children and adolescents with LLCs and SPMI were analyzed through correlation coefficients and Mann-Whitney U testing. The results confirmed the consistency of both sources of information. The highest levels of agreements with the global rating were achieved for disturbances in terms of going to sleep and disturbances with respect to remaining asleep. The results demonstrate that the scales and therefore the SNAKE itself is well-suited for gathering information on different sleep(-associated) problems in this vulnerable population.

Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.

Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.

Spontaneous recurrent episodes of wrist pain in a 16-year-old girl: a case of complex regional pain syndrome.

Introduction: Complex regional pain syndromes (CRPS) are disabling pain syndromes that can develop after minor tissue injury or trauma and are characterized by sensory, motor, and autonomic abnormalities distributed in a glove-like or stocking-like manner. Complex regional pain syndrome is well known in adults, but is relatively rare in children. Most of the reported cases of CRPS in children are clinical diagnoses that are not supported by examinations such as three-phase bone scintigraphy. Furthermore, different centres often use different diagnostic criteria for CRPS, which sometimes questions the diagnosis of CRPS. Objective/Methods: Although, recurrences and in particular relapses of CRPS have been observed, a periodically, nearly self-limiting course of disease without any residues in pain-free episodes and without any new obvious injury in CRPS is rather unusual. We present the case of a 16-year-old girl who reported recurrent spontaneous pain which lasted for 2 to 3 weeks and occurred approximately 2 times a year after the patient had experienced a mild trauma 3 years ago. Results: The pain was accompanied by swelling, temperature asymmetry, and decreased range of motion of the right hand without any complains in pain-free episodes. Recurrent symptoms occurred without any obvious trauma. Diagnosis of CRPS was made from clinical findings including quantitative sensory testing, increased periarticular radioisotope uptake in the delayed phase of three-phase bone scintigraphy and examination during anaesthesia. Multimodal inpatient pain treatment resolved her symptoms substantially. Conclusion: Complex regional pain syndrome in children may imitate rheumatologic diseases, and the course is different from adults despite similar clinical findings.

Overcoming pain thresholds with multilevel models-an example using quantitative sensory testing (QST) data.

The assessment of somatosensory function is a cornerstone of research and clinical practice in neurology. Recent initiatives have developed novel protocols for quantitative sensory testing (QST). Application of these methods led to intriguing findings, such as the presence lower pain-thresholds in healthy children compared to healthy adolescents. In this article, we (re-) introduce the basic concepts of signal detection theory (SDT) as a method to investigate such differences in somatosensory function in detail. SDT describes participants' responses according to two parameters, sensitivity and response-bias. Sensitivity refers to individuals' ability to discriminate between painful and non-painful stimulations. Response-bias refers to individuals' criterion for giving a "painful" response. We describe how multilevel models can be used to estimate these parameters and to overcome central critiques of these methods. To provide an example we apply these methods to data from the mechanical pain sensitivity test of the QST protocol. The results show that adolescents are more sensitive to mechanical pain and contradict the idea that younger children simply use more lenient criteria to report pain. Overall, we hope that the wider use of multilevel modeling to describe somatosensory functioning may advance neurology research and practice.

Pain hypersensitivity in juvenile idiopathic arthritis: a quantitative sensory testing study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common cause of non-infectious joint inflammation in children. Synovial inflammation results in pain, swelling and stiffness. Animal and adult human studies indicate that localized joint-associated inflammation may produce generalized changes in pain sensitivity. The aim was to characterize pain sensitivity in children with JIA to mechanical and thermal stimulus modalities using quantitative sensory testing (QST) at an affected inflamed joint, and compare to children in clinical remission. Generalized hypersensitivity was evaluated by comparing QST measures at the thenar eminence between JIA and healthy control children. METHODS: 60 children aged 7-17 years with JIA participated. QST assessed sensory detection threshold and pain threshold at two sites: (1) affected joint (clinically active or inactive), (2) contralateral thenar eminence. Joint site included finger, wrist, knee and ankle. Clinical status was measured using objective and subjective markers of disease severity. Questionnaires assessed pain intensity and frequency, functional disability, anxiety, pain catastrophization and fatigue. QST data collected from joints were compared within JIA patients: active vs. inactive inflammation; and data from the contralateral thenar eminence were compared between JIA and healthy control cohorts in Europe [EU, (n = 151)] and the US (n = 92). Statistical analyses were performed using Kruskal-Wallis with Dunn's post-hoc comparison, Mann-Whitney or Fisher's exact test, where appropriate. RESULTS: Overall, children with JIA reported low pain scores and low degrees of functional disability. Sensory detection thresholds and pain thresholds were similar in "active" compared to "inactive" joints. Despite this, children with JIA had generalized hypersensitivity at the thenar eminence when compared to healthy children for pressure (vs. EU p < 0.001), light touch (vs. EU p < 0.001), cold (vs EU, p < 0.01; vs US, p < 0.001) and heat pain (vs EU, p < 0.05; vs US p < 0.001). CONCLUSIONS: JIA is associated with increased sensitivity to painful mechanical and thermal stimuli, even in absence of pain reports, or markers of disease activity. Future research investigating mechanisms underlying pain hypersensitivity in JIA is warranted; this will in turn guide pharmacologic and non-pharmacologic interventions to prevent or reverse these processes.