2024-03-28T12:03:23Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/291872021-06-24T07:36:36Zcom_10324_32522com_10324_952com_10324_894com_10324_43677com_10324_954com_10324_1134com_10324_931col_10324_32523col_10324_43678col_10324_1213
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
López López, José Ramón
Alpizar, Yeranddy A.
Meseguer, Víctor
Enoch, Luis
Tajada Esteban, 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
Producción Científica
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.
2018-03-23
2018-03-23
2014
info:eu-repo/semantics/article
Nature Communications, 2014, vol. 5. p. 1-16
2041-1723
http://uvadoc.uva.es/handle/10324/29187
10.1038/ncomms4125
1
16
Nature Communications
5
eng
https://www.nature.com/articles/ncomms4125
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
Macmillan Publishers