title: Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain.
abstract: OBJECTIVE
  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.
authors: Correspondence to Dr Andrew D Cook, Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Parkville, VC 3010, Australia. adcook@unimelb.edu.au
authors: Andrew D
authors: AD
authors: Cook
authors: Jarrad
authors: J
authors: Pobjoy
authors: Shannon
authors: S
authors: Sarros
authors: Stefan
authors: S
authors: Steidl
authors: Manuela
authors: M
authors: Dürr
authors: Derek C
authors: DC
authors: Lacey
authors: John A
authors: JA
authors: Hamilton
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000378:metabolism; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000209:etiology / Q000378:metabolism*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor