RT info:eu-repo/semantics/article
T1 TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
A1 Meseguer, Victor
A1 Alpizar, Yeranddy A.
A1 Luis, Enoch
A1 Tajada, Sendoa
A1 Denlinger, Bristol
A1 Fajardo, Otto
A1 Manenschijn, Jan-Albert
A1 Fernández-Peña, Carlos
A1 Talavera, Arturo
A1 Kichko, Tatiana
A1 Navia, Belén
A1 Sánchez, Alicia
A1 Señarís, Rosa
A1 Reeh, Peter
A1 Pérez-García, María Teresa
A1 López-López, José Ramón
A1 Voets, Thomas
A1 Belmonte, Carlos
A1 Talavera, Karel
A1 Viana, Félix
AB Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.
YR 2014
FD 2014
LK https://uvadoc.uva.es/handle/10324/65782
UL https://uvadoc.uva.es/handle/10324/65782
LA spa
NO Nat Commun. 2014;5:3125.
DS UVaDOC
RD 29-nov-2024