title: Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: in vivo study using TRPA1-deficient mice.
abstract: BACKGROUND
  The transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable cation channel that is expressed on capsaicin-sensitive sensory neurons, endothelial and inflammatory cells. It is activated by a variety of inflammatory mediators, such as methylglyoxal, formaldehyde and hydrogen sulphide. Since only few data are available about the role of TRPA1 in arthritis and related pain, we investigated its involvement in inflammation models of different mechanisms.
  
  
  METHODS
  Chronic arthritis was induced by complete Freund's adjuvant (CFA), knee osteoarthritis by monosodium iodoacetate (MIA) in TRPA1 knockout (KO) mice and C57Bl/6 wildtype mice. For comparison, carrageenan- and CFA-evoked acute paw and knee inflammatory changes were investigated. Thermonociception was determined on a hot plate, cold tolerance in icy water, mechanonociception by aesthesiometry, paw volume by plethysmometry, knee diameter by micrometry, weight distribution with incapacitance tester, neutrophil myeloperoxidase activity and vascular leakage by in vivo optical imaging, and histopathological alterations by semiquantitative scoring.
  
  
  RESULTS
  CFA-induced chronic mechanical hypersensitivity, tibiotarsal joint swelling and histopathological alterations, as well as myeloperoxidase activity in the early phase (day 2), and vascular leakage in the later stage (day 7), were significantly reduced in TRPA1 KO mice. Heat and cold sensitivities did not change in this model. Although in TRPA1 KO animals MIA-evoked knee swelling and histopathological destruction were not altered, hypersensitivity and impaired weight bearing on the osteoarthritic limb were significantly decreased. In contrast, carrageenan- and CFA-induced acute inflammation and pain behaviours were not modified by TRPA1 deletion.
  
  
  CONCLUSIONS
  TRPA1 has an important role in chronic arthritis/osteoarthritis and related pain behaviours in the mouse. Therefore, it might be a promising target for novel analgesic/anti-inflammatory drugs.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. hadam20@gmail.com.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. hadam20@gmail.com.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. hadam20@gmail.com.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Horváth
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. valeria.tekus@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. valeria.tekus@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. valeria.tekus@aok.pte.hu.
authors.forename: Valéria
authors.initials: V
authors.lastname: Tékus
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. mboroslinda@gmail.com.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. mboroslinda@gmail.com.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. mboroslinda@gmail.com.
authors.forename: Melinda
authors.initials: M
authors.lastname: Boros
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. gabor.pozsgai@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. gabor.pozsgai@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. gabor.pozsgai@aok.pte.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Pozsgai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. balint.botz@gmail.com.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. balint.botz@gmail.com.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. balint.botz@gmail.com.
authors.forename: Bálint
authors.initials: B
authors.lastname: Botz
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. eva.borbely@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. eva.borbely@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. eva.borbely@aok.pte.hu.
authors.forename: Éva
authors.initials: É
authors.lastname: Borbély
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. janos.szolcsanyi@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. janos.szolcsanyi@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. janos.szolcsanyi@aok.pte.hu.|PharmInVivo Ltd., 10 Szondi György Street, Pécs, 7624, Hungary. janos.szolcsanyi@aok.pte.hu.
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. erika.pinter@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. erika.pinter@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. erika.pinter@aok.pte.hu.|PharmInVivo Ltd., 10 Szondi György Street, Pécs, 7624, Hungary. erika.pinter@aok.pte.hu.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, 12 Szigeti Street, Pécs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.|János Szentágothai Research Centre, University of Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.|Centre of Neuroscience, University of Pécs, Medical School, Pécs, 20 Ifjúság Street, Pécs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.|PharmInVivo Ltd., 10 Szondi György Street, Pécs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.|MTA-PTE NAP B Chronic Pain Research Group, 12 Szigeti Street, Pécs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology*; D002908:Chronic Disease; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000172:deficiency*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse