title: Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain.
abstract: BACKGROUND
  Chronic pain arising from degenerative diseases of the joint such as osteoarthritis (OA) has a strong peripheral component which is likely to be mediator driven. Current treatments which reduce the production of such mediators i.e. non-steroidal anti-inflammatory drugs (NSAIDs), can help to lessen pain in OA patients. However, this is not always the case and complete pain relief is rarely achieved, suggesting that additional unidentified mediators play a role. Here we have investigated the notion that chemokines might act as such pain mediators in OA.
  
  
  RESULTS
  Using the monosodium iodoacetate (MIA) model of chronic joint pain the expression of over 90 different inflammatory mediators, mainly cytokines and chemokines, were measured in tissues taken from the femorotibial joint (cartilage, subchondral bone, fat pad) using custom-made quantitative real-time polymerase chain reaction (qPCR) array cards. At both the day 3 and 14 time points, numerous inflammatory mediators were significantly up-regulated in these tissues, although it was clear that the largest transcriptional dysregulation occurred in the cartilage. Using individual qPCR to measure immune cell markers, a significant infiltration of macrophages was measured in the cartilage and fat pad at day 3. Neutrophil infiltration was also measured in the fat pad at the same time point, but no infiltration was observed at day 14. Combination of mRNA expression data from different time points and tissues identified the chemokines, CCL2, 7 and 9 as being consistently up-regulated. The overall increase in CCL2 expression was also measured at the protein level.
  
  
  CONCLUSIONS
  Chemokines in general and CCL2, 7 and 9 in particular, represent promising targets for further studies into the identification of new pain mediators in chronic joint pain.
authors.affiliation: Nuffield Department of Clinical Neurosciences, West Wing, Level 6, John Radcliffe Hospital, Oxford OX3 9DU, UK. john.dawes@ndcn.ox.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Dawes
authors.forename: Hannes
authors.initials: H
authors.lastname: Kiesewetter
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennett
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D018932:Chemokine CCL2 / Q000378:metabolism; D054410:Chemokine CCL7 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007461:Iodoacetates / Q000494:pharmacology / Q000627:therapeutic use*; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: C510551:CCL9 protein, rat; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D007461:Iodoacetates