TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Open accessAbstract
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.
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Recent evidences have linked activation of TLRs, particularly TLR-4, with changes in nociception.
“Recent evidences have linked activation of TLRs, particularly TLR-4, with changes in nociception.47,48”
From Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice (2015) · cites this paper as [47]
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- Authors
- Meseguer, V., Alpizar, Y. A., Luis, E., Tajada, S., Denlinger, B., Fajardo, O., Manenschijn, J.-A., Fernández-Peña, C., Talavera, A., Kichko, T., Navia, B., Sánchez, A., Señarís, R., Reeh, P., Pérez-García, M. T., López-López, J. R., Voets, T., Belmonte, C., Talavera, K., & Viana, F.
- Affiliations
- KU Leuven (BE)
- Instituto de Neurociencias (ES)
- Universidad de Valladolid (ES)
- Finlay Institute (CU)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Universidade de Santiago de Compostela (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Viana, Félix
- ORCID
- Venue
- Nature Communications
- Published
- 2014-01-20
- Volume
- 5
- Issue
- 1
- Pages
- 3125-3125
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3905718
- OpenAlex
- W2103447688
- Cited by
- 479
- References
- 69
- Citations by year
- 2026: 35 · 2025: 38 · 2024: 42 · 2023: 39 · 2022: 35 · 2021: 61 · 2020: 50 · 2019: 41 · 2018: 26 · 2017: 36 · 2016: 36 · 2015: 26 · 2014: 10 · 2013: 1
- FWCI
- 22.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- University of Valladolid Documentary Repository (University of Valladolid) (submittedVersion, cc-by-nc-nd)
- University of Valladolid Documentary Repository (University of Valladolid) (submittedVersion, other-oa)
- Funders
- Australian Government
- Generalitat Valenciana
- KU Leuven (GOA 2009/07, P7/13, OT/12/091, P6/28, PFV/10/006, EF/95/010)
- Vlaamse regering
- Instituto de Salud Carlos III (00023)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Keywords
- TRPA1, neurogenic inflammation, pain, lipopolysaccharide, TLR4, nociceptor sensitization, CGRP release, bacterial endotoxin, gram-negative bacterial infection, vascular response, nociceptors
- MeSH terms
- TRPA1 Cation Channel, Animals, Cell Membrane, Cricetulus, Escherichia coli, Cricetinae, Humans, Lipid A, Lipopolysaccharides, Membrane Potentials, Mice, Inbred C57BL, Neuropeptides, Nociceptors, Pain, Sensory Receptor Cells, Signal Transduction, Ion Channel Gating, CHO Cells, Mice, Knockout, Neurogenic Inflammation, Transient Receptor Potential Channels, Toll-Like Receptor 4, HEK293 Cells
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