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Title: TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Authors: López López, José Ramón
Alpizar, Yeranddy A.
Meseguer, Víctor
Enoch, Luis
Tajada, Sendoa
Denlinger, Bristol
Fajardo, Otto
Manenschijn, Jan-Albert
Fernández Peña, Carlos
Talavera, Arturo
Kichko, Tatiana
Navia, Belén
Sánchez, Alicia
Señarís, Rosa
Reeh, Peter
Pérez García, María Teresa
Voets, Thomas
Belmonte, Carlos
Talavera, Karel
Viana, Felix
Issue Date: 2014
Publisher: Macmillan Publishers
Description: Producción Científica
Citation: Nature Communications, 2014, vol. 5. p. 1-16
Abstract: 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.
Classification: Infección bacteriana
ISSN: 2041-1723
Peer Review: SI
DOI: https://doi:10.1038/ncomms4125
Sponsor: Projects SAF2010-14990 and PROMETEO2010-046. Instituto de Salud Carlos III. CONSOLIDER-INGENIO 2010. ISCIII grants R006/009 (Red Heracles), the Spanish Fundación Marcelino Botín and Belgian Federal Government (IUAP P6/28 and P7/13), the Research Foundation-Flanders and the Research Council of the KU Leuven.
Publisher Version:
Language: eng
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:DEP06 - Artículos de revista

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