Journal Club 2014.12.29

TRPA1 channels mediate acute neurogenic
inflammation and pain produced by bacterial
endotoxins
Victor Meseguer1
, Yeranddy A. Alpizar2, Enoch Luis1
, Sendoa Tajada3, Bristol Denlinger1
, Otto Fajardo1
,Jan-Albert Manenschijn1
, Carlos Ferna´ndez-Pen˜a1
, Arturo Talavera2,4, Tatiana Kichko5, Bele´n Navia6,
Alicia Sa´nchez2, Rosa Sen˜arı´s6, Peter Reeh5, Marı´a Teresa Pe´rez-Garcı´a3, Jose´ Ramo´n Lo´pez-Lo´pez3,
Thomas Voets2, Carlos Belmonte1
, Karel Talavera1,2,* & Fe´lix Viana1,*

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.