title: Pain hypersensitivity in juvenile idiopathic arthritis: a quantitative sensory testing study.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cornelissen
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Donado
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kim
authors.affiliation: Program in Rheumatology, Division of Immunology, Department of Medicine, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School Boston, Boston, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Chiel
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA ; Department of Psychiatry, Harvard Medical School, Boston, USA.
authors.forename: Deirdre E
authors.initials: DE
authors.lastname: Logan
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Meier
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Navil F
authors.initials: NF
authors.lastname: Sethna
authors.affiliation: Department of Pediatric Neurology, Psychosomatic Medicine and Pain Therapy, Center for Child and Adolescent Medicine Olgahospital, Klinikum, Stuttgart, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Blankenburg
authors.affiliation: German Paediatric Pain Centre, Children's and Adolescents' Hospital, Datteln; Chair of Children's Pain Therapy and Paediatric Palliative Care, Witten/Herdecke University, Datteln, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Zernikow
authors.affiliation: Program in Rheumatology, Division of Immunology, Department of Medicine, Boston Children's Hospital; Department of Pediatrics, Harvard Medical School Boston, Boston, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Sundel
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital; Department of Anesthesia, Harvard Medical School, 333 Longwood Avenue, Boston, MA 02115 USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Berde
mesh_terms: D000293:Adolescent; D018771:Arthralgia / Q000453:epidemiology* / Q000209:etiology; D001171:Arthritis, Juvenile / Q000150:complications / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008297:Male; D010147:Pain Measurement; D058748:Pain Perception / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation; D015995:Prevalence; D012684:Sensory Thresholds / Q000502:physiology; D013001:Somatoform Disorders / Q000453:epidemiology* / Q000209:etiology
keywords: Arthritis; Hyperalgesia; Inflammation; Pain; Quantitative sensory testing, Children, Adolescents; Somatosensory profile