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 10-oct-2024