Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: In vivo study using TRPA1-deficient mice

Ádám Horváth, Valéria Tékus, Melinda Boros, Gábor Pozsgai, Bálint Botz, Éva Borbély, János Szolcsányi, Erika Pintér, Zsuzsanna Helyes

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38 Citations (Scopus)

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.

Original languageEnglish
Article number6
JournalArthritis Research and Therapy
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 8 2016

Keywords

  • Adjuvant-induced arthritis
  • Carrageenan-induced acute inflammation
  • Hypersensitivity
  • In vivo optical imaging
  • MIA-induced osteoarthritis
  • Oedema
  • Pain
  • TRPA1 receptor-deficient mice

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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