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Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain
  1. Andrew D Cook1,
  2. Jarrad Pobjoy1,
  3. Shannon Sarros1,
  4. Stefan Steidl2,
  5. Manuela Dürr2,
  6. Derek C Lacey1,
  7. John A Hamilton1
  1. 1Department of Medicine, Arthritis and Inflammation Research Centre, University of Melbourne, Victoria, Australia
  2. 2MorphoSys AG, Martinsried/Planegg, Germany
  1. Correspondence to Dr Andrew D Cook, Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Parkville, VC 3010, Australia; adcook{at}unimelb.edu.au

Abstract

Objectives Better therapies are needed for inflammatory pain. In arthritis the relationship between joint pain, inflammation and damage is unclear. Granulocyte-macrophage colony-stimulating factor (GM–CSF) is important for the progression of a number of inflammatory/autoimmune conditions including arthritis; clinical trials targeting its action in rheumatoid arthritis are underway. However, its contribution to inflammatory and arthritic pain is unknown. The aims of this study were to determine whether GM–CSF controls inflammatory and/or arthritic pain.

Methods A model of inflammatory pain (complete Freund's adjuvant footpad), as well as two inflammatory arthritis models, were induced in GM–CSF−/− mice and development of pain (assessment of weight distribution) and arthritic disease (histology) was assessed. Pain was further assessed in a GM–CSF-driven arthritis (methylated bovine serum albumin/GM–CSF) model and the cyclooxygenase-dependence determined using indomethacin.

Results GM–CSF was absolutely required for pain development in both the inflammatory pain and arthritis models, including for IL-1-dependent arthritic pain. Pain in a GM–CSF-driven arthritis model, but not the disease itself, was abolished by the cyclooxygenase inhibitor, indomethacin, indicating separate pathways downstream of GM–CSF for pain and arthritis control.

Conclusions GM–CSF is key to the development of inflammatory and arthritic pain, suggesting that pain alleviation could result from trials evaluating its role in inflammatory/autoimmune conditions.

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Footnotes

  • Funding This work was supported by grants from Morphosys AG and the National Health and Medical Research Council (NHMRC), and by a NHMRC Senior Principal Research Fellowship (JAH).

  • Competing interests SSt is a full-time employee of MorphoSys AG, Germany. JAH has received consulting fees from MorphoSys AG, Germany (less than US$10 000 a year). The University of Melbourne has licensed to MorphoSys AG, Germany, patented technology relating to therapeutically targeting granulocyte-macrophage colony-stimulating factor, for which licensing fees and milestone payments have been made. The other authors state no conflict of interests.

  • Ethics approval All experiments were approved by the University of Melbourne Animal Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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