Tese
Participação do receptor TRPA1 em modelos de ataque agudo de gota em roedores
Fecha
2013-10-21Registro en:
SANTOS, Gabriela Trevisan dos. Participation of TRPA1 receptor in acute gout attack models in rodents. 2013. 135 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2013.
Autor
Santos, Gabriela Trevisan dos
Institución
Resumen
Gout is a prevalent form of inflammatory arthritis, which leads to patients poor quality
of life. Acute gout attacks produce severe joint pain and inflammation associated with
oxidative stress induction. This pathology is provoked by the accumulation of monosodium
urate (MSU) crystals, but the underlying pain mechanisms in acute gout attacks are still
poorly understood. The transient potential receptor ankyrin 1 (TRPA1) is a sensor for
endogenous oxidant compounds, such as hydrogen peroxide (H2O2), found in peptidergic
sensory fibers associated to inflammatory pain. The goal of this study was to explore the
TRPA1 role in two models of monosodium urate (MSU) crystals-induced inflammation and
nociception in rats and mice. We found that TRPA1 antagonism (HC-030031 or camphor),
TRPA1 gene deletion or defunctionalization by capsaicin pretreatment of peptidergic TRPexpressing
primary sensory neurons markedly decreased MSU-induced nociception and
edema after intraplantar (i.pl.) or intra-articular (i.a.) injection. In addition to these neurogenic
effects, MSU increased H2O2 levels in the injected tissue, an effect that was abolished by the
H2O2-detoxifing, catalase enzyme. TRPA1 immunoreactivity in sciatic nerve and the levels of
calcitonin gene related peptide (CGRP) in the synovial tissue were also increased by MSU.
H2O2 i.pl. or i.a. injection mimicked MSU, causing nociception and edema prevented by
TRPA1 antagonism. Moreover, TRPA1 blockage abrogated the increase in neutrophil
infiltration and interleukin-1β elicited by MSU. Our results suggest that MSU-injection
increases tissue H2O2 thereby stimulating TRPA1 on sensory nerve endings to produce
inflammation and nociception. Thus, TRPA1 may be explored as a valuable target in acute
gout management.