A multidisciplinary assessment of pain in juvenile idiopathic arthritis

Jaymin Upadhyay*, Jordan Lemme, Mariesa Cay, Hanne Van Der Heijden, Diana Sibai, Benjamin Goodlett, Jeffery Lo, Kacie Hoyt, Maria Taylor, Melissa M. Hazen, Olha Halyabar, Esra Meidan, Rudy Schreiber, Margaret H. Chang, Peter A. Nigrovic, Camilo Jaimes, Lauren A. Henderson, Kirsten Ecklund, Robert P. Sundel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction: Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA. Methods: 16 male and female JIA patients (12.7 2.8 years of age) on active treatment were enrolled, together with age-and sex-matched controls. Patients were assessed using physical examination, clinical questionnaires, musculoskeletal MRI, and structural neuroimaging. In addition, functional magnetic resonance imaging (fMRI) data were collected during the resting-state, hand-motor task performance, and cold stimulation of the hand and knee. Results: Patients with and without pain and with and without inflammation (joint and systemic) were evaluated. Pain severity was associated with more physical stress and poorer cognitive function. Corrected for multiple comparisons, morphological analysis revealed decreased cortical thickness within the insula cortex and a negative correlation between caudate nucleus volume and pain severity. Functional neuroimaging findings suggested alteration within neurocircuitry structures regulating emotional pain processing (anterior insula) in addition to the default-mode and sensorimotor networks. Conclusions: Patients with JIA may exhibit changes in neurobiological circuits related to pain. These preliminary findings suggest mechanisms by which pain could potentially become dissociated from detectable joint pathology and persist independently of inflammation or treatment status. (c) 2021 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)700-711
Number of pages12
JournalSeminars in Arthritis and Rheumatism
Issue number4
Publication statusPublished - Aug 2021


  • Juvenile idiopathic arthritis
  • Pain
  • Inflammation
  • Voxel-based morphometry
  • Functional magnetic resonance imaging
  • Musculoskeletal
  • Anterior insula
  • Caudate
  • HEAT

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