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  • Review Article
  • Published:

Neural mechanisms underlying the pain of juvenile idiopathic arthritis

Nature Reviews Rheumatology volume 10, pages 205–211 (2014)Cite this article

Subjects

Key Points

  • Pain is the most common and distressing symptom of juvenile idiopathic arthritis (JIA) and can persist despite good disease control

  • Effective pain management in patients with JIA will benefit from an understanding of the special features of pain processing in the juvenile nervous system

  • Persistent pain is maintained by functional changes in the peripheral and central nervous systems, which depend upon age at onset

  • Animal models show that exposure to injury, pain and stress in early life 'primes' the pain system, such that adult tissue injury and inflammation is more painful

  • Effective age-appropriate treatment of JIA pain is therefore probably of lifelong benefit

Abstract

Pain is the most common symptom of juvenile idiopathic arthritis (JIA) and is arguably a more important factor in disability than the progression of the disease itself. Studies have highlighted the extent of this pain and its persistence in some young patients despite effective disease control. Understandingand effective management of pain in JIA is limited, and improved diagnosis and treatment would benefit from increased knowledge of the mechanisms underlying pain in childhood. This Review focuses upon the developmental neurobiology of pain, reviewing studies in animal models that increase clinical understanding and inform treatment of the painful manifestations of JIA. Pain processing in the juvenile nervous system differs from that in adults: nociceptive thresholds are lower and endogenous pain control systems are slow to mature. Furthermore, increasing evidence points to tissue injury in childhood having prolonged effects upon the developing pain system. Injury, inflammation and stress in early life can 'prime' peripheral nociceptors and central pain circuits, such that the pain associated with tissue inflammation is exacerbated in later life. A developmental, mechanism-based approach towards developing novel targets for the treatment of pain in JIA might therefore benefit the patient both as a child and as an adult if the disease recurs or persists.

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Figure 1: Effects on the pain pathway of joint inflammation in early life.

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Acknowledgements

M.F. and L.L.H.d.L are supported by an MRC UK grant (ref: G0901269). Y.I. is supported through an Arthritis Research UK grant (ref: 20164) and is also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

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Authors and Affiliations

  1. Department of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK

    Luke La Hausse de Lalouvière & Maria Fitzgerald

  2. Arthritis Research UK Centre for Adolescent Rheumatology, University College London (UCL), UCL Hospital and Great Ormond Street Hospital, London, WC1E 6JF, UK

    Yiannis Ioannou

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Correspondence to Maria Fitzgerald.

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de Lalouvière, L., Ioannou, Y. & Fitzgerald, M. Neural mechanisms underlying the pain of juvenile idiopathic arthritis. Nat Rev Rheumatol 10, 205–211 (2014). https://doi.org/10.1038/nrrheum.2014.4

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