PubMed 24780252

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: TRPA1 receptor stimulation by hydrogen peroxide is critical to trigger hyperalgesia and inflammation in a model of acute gout.

Authors: Gabriela Trevisan, Carin Hoffmeister, Mateus Fortes Rossato, Sara Marchesan Oliveira, Mariane Arnoldi Silva, Cássia Regina Silva, Camilla Fusi, Raquel Tonello, Daiana Minocci, Gustavo Petri Guerra, Serena Materazzi, Romina Nassini, Pierangelo Geppetti, Juliano Ferreira

Journal, date & volume: Free Radic. Biol. Med., 2014 Jul , 72, 200-9

PubMed link:

Acute gout attacks produce severe joint pain and inflammation associated with monosodium urate (MSU) crystals leading to oxidative stress production. The transient potential receptor ankyrin 1 (TRPA1) is expressed by a subpopulation of peptidergic nociceptors and, via its activation by endogenous reactive oxygen species, including hydrogen peroxide (H2O2), contributes to pain and neurogenic inflammation. The aim of this study was to investigate the role of TRPA1 in hyperalgesia and inflammation in a model of acute gout attack in rodents. Inflammatory parameters and mechanical hyperalgesia were measured in male Wistar rats and in wild-type (Trpa1(+/+)) or TRPA1-deficient (Trpa1(-/-)) male mice. Animals received intra-articular (ia, ankle) injection of MSU. The role of TRPA1 was assessed by receptor antagonism, gene deletion or expression, sensory fiber defunctionalization, and calcitonin gene-related peptide (CGRP) release. We found that nociceptor defunctionalization, TRPA1 antagonist treatment (via ia or oral administration), and Trpa1 gene ablation abated hyperalgesia and inflammatory responses (edema, H2O2 generation, interleukin-1β release, and neutrophil infiltration) induced by ia MSU injection. In addition, we showed that MSU evoked generation of H2O2 in synovial tissue, which stimulated TRPA1 producing CGRP release and plasma protein extravasation. The MSU-elicited responses were also reduced by the H2O2-detoxifying enzyme catalase and the reducing agent dithiothreitol. TRPA1 activation by MSU challenge-generated H2O2 mediates the entire inflammatory response in an acute gout attack rodent model, thus strengthening the role of the TRPA1 receptor and H2O2 production as potential targets for treatment of acute gout attacks.