TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Víctor M. Meseguer,Yeranddy A. Alpizar,Enoch Luis,Sendoa Tajada,Bristol Denlinger,Otto Fajardo,Jan-Albert Manenschijn,Carlos Fernández-Peña,Arturo Talavera,Tatiana Kichko,Belén Navia,Alicia Sanchez,Rosa Señarís,Peter W. Reeh,M. T. Pérez-García,José R. López-López,Thomas Voets,Carlos Belmonte,Karel Talavera,Félix Viana +19 more
Reads0
Chats0
TLDR
This work shows 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, and finds that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent onTRPA1 channel activation in nocICEptive sensory neurons, and develop independently of TLR4 activation.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.read more
Citations
More filters
Journal ArticleDOI
Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation.
TL;DR: The dialog between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic, and a better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases.
Journal ArticleDOI
Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages
Ilana Gabanyi,Paul A. Muller,Linda Feighery,Thiago Y. Oliveira,Frederico Azevedo da Costa-Pinto,Frederico Azevedo da Costa-Pinto,Daniel Mucida +6 more
TL;DR: The results reveal unique intra-tissue macrophage specialization and identify neuro-immune communication between enteric neurons and macrophages that induces rapid tissue-protective responses to distal perturbations.
Journal ArticleDOI
Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine
Bernd Nilius,Arpad Szallasi +1 more
TL;DR: An overview of the functional properties of mammalian TRP channels is given, their roles in acquired and hereditary diseases are described, and their potential as drug targets for therapeutic intervention is discussed.
Journal ArticleDOI
TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization
Olivier Gouin,Killian L’Herondelle,Nicolas Lebonvallet,Christelle Le Gall-Ianotto,Mehdi Sakka,Virginie Buhé,Emmanuelle Plée-Gautier,Jean-Luc Carré,Luc Lefeuvre,Laurent Misery,Raphaele Le Garrec +10 more
TL;DR: The role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells is discussed.
Journal ArticleDOI
Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration.
Carla R.A. Batista,Giovanni Freitas Gomes,Eduardo Candelario-Jalil,Bernd L. Fiebich,Antônio Carlos Pinheiro de Oliveira +4 more
TL;DR: The use of LPS in various models of neurodegeneration is reviewed as well as the neuroinflammatory mechanisms induced by this toxin that could underpin the pathological events linked to the Neurodegenerative process are discussed.
References
More filters
Journal ArticleDOI
Pathogen Recognition and Innate Immunity
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
Journal ArticleDOI
Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Journal ArticleDOI
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,C. Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Suva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,B. Layton,Bruce Beutler +13 more
Journal ArticleDOI
Quantitative assessment of tactile allodynia in the rat paw.
TL;DR: Threshold measurement using the up-down paradigm, in combination with the neuropathy pain model, represents a powerful tool for analyzing the effects of manipulations of the neuropathic pain state.