title: Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice--potential role of TRPA1 in osteoarthritis.
abstract: OBJECTIVE
  Intra-articularly injected monosodium iodoacetate (MIA) induces joint pathology mimicking osteoarthritis (OA) and it is a widely used experimental model of OA. MIA induces acute inflammation, cartilage degradation and joint pain. Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation. Here, we tested the hypothesis that TRPA1 would be involved in the development of MIA-induced acute inflammation, cartilage changes and joint pain.
  
  
  METHODS
  The effects of pharmacological blockade (by TCS 5861528) and genetic depletion of TRPA1 were studied in MIA-induced acute paw inflammation. Cartilage changes (histological scoring) and joint pain (weight-bearing test) in MIA-induced experimental OA were compared between wild type and TRPA1 deficient mice. The effects of MIA were also studied in primary human OA chondrocytes and in mouse cartilage.
  
  
  RESULTS
  MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice. Interestingly, these responses were attenuated in TRPA1 deficient animals. MIA-induced paw inflammation was associated with increased tissue levels of substance P; and the inflammatory edema was reduced by pretreatment with catalase, with the TRPA1 antagonist TCS 5861528 and with the neurokinin 1 receptor antagonist L703,606. In chondrocytes, MIA enhanced interleukin-1 induced cyclooxygenase-2 (COX-2) expression, an effect that was blunted by pharmacological inhibition and genetic depletion of TRPA1.
  
  
  CONCLUSIONS
  TRPA1 was found to mediate acute inflammation and the development of degenerative cartilage changes and joint pain in MIA-induced experimental OA in the mouse. The results reveal TRPA1 as a potential mediator and drug target in OA.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: lauri.j.moilanen@uta.fi.
authors.forename: L J
authors.initials: LJ
authors.lastname: Moilanen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: mari.j.hamalainen@uta.fi.
authors.forename: M
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: elina.nummenmaa@uta.fi.
authors.forename: E
authors.initials: E
authors.lastname: Nummenmaa
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: pinja.ilmarinen@uta.fi.
authors.forename: P
authors.initials: P
authors.lastname: Ilmarinen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: katriina.vuolteenaho@uta.fi.
authors.forename: K
authors.initials: K
authors.lastname: Vuolteenaho
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: riina.m.nieminen@uta.fi.
authors.forename: R M
authors.initials: RM
authors.lastname: Nieminen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: lauri.lehtimaki@uta.fi.
authors.forename: L
authors.initials: L
authors.lastname: Lehtimäki
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: eeva.moilanen@uta.fi.
authors.forename: E
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000818:Animals; D018771:Arthralgia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007269:Injections, Intra-Arterial; D019807:Iodoacetic Acid / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D004247:DNA; D019807:Iodoacetic Acid
keywords: COX-2; Inflammation; Joint pain; Monosodium iodoacetate-induced osteoarthritis; TRPA1