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Citations to this article

The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons
Andreas Leffler, … , Peter W. Reeh, Carla Nau
Andreas Leffler, … , Peter W. Reeh, Carla Nau
Published January 2, 2008
Citation Information: J Clin Invest. 2008;118(2):763-776. https://doi.org/10.1172/JCI32751.
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Research Article Neuroscience Article has an altmetric score of 1

The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons

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Abstract

Local anesthetics (LAs) block the generation and propagation of action potentials by interacting with specific sites of voltage-gated Na+ channels. LAs can also excite sensory neurons and be neurotoxic through mechanisms that are as yet undefined. Nonspecific cation channels of the transient receptor potential (TRP) channel family that are predominantly expressed by nociceptive sensory neurons render these neurons sensitive to a variety of insults. Here we demonstrated that the LA lidocaine activated TRP channel family receptors TRPV1 and, to a lesser extent, TRPA1 in rodent dorsal root ganglion sensory neurons as well as in HEK293t cells expressing TRPV1 or TRPA1. Lidocaine also induced a TRPV1-dependent release of calcitonin gene–related peptide (CGRP) from isolated skin and peripheral nerve. Lidocaine sensitivity of TRPV1 required segments of the putative vanilloid-binding domain within and adjacent to transmembrane domain 3, was diminished under phosphatidylinositol 4,5-bisphosphate depletion, and was abrogated by a point mutation at residue R701 in the proximal C-terminal TRP domain. These data identify TRPV1 and TRPA1 as putative key elements of LA-induced nociceptor excitation. This effect is sufficient to release CGRP, a key component of neurogenic inflammation, and warrants investigation into the role of TRPV1 and TRPA1 in LA-induced neurotoxicity.

Authors

Andreas Leffler, Michael J. Fischer, Dietlinde Rehner, Stephanie Kienel, Katrin Kistner, Susanne K. Sauer, Narender R. Gavva, Peter W. Reeh, Carla Nau

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 2 3 1 5 7 4 2 4 5 4 3 7 1 4 3 5 2 62
Citation information
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Citations to this article in year 2014 (3)

Title and authors Publication Year
TRP Channels Involved in Spontaneous L-Glutamate Release Enhancement in the Adult Rat Spinal Substantia Gelatinosa
E Kumamoto, T Fujita, CY Jiang
Cells 2014
Coapplication of Lidocaine and Membrane-Impermeable Lidocaine Derivative QX-222 Produces Divergent Effects on Evoked and Spontaneous Nociceptive Behaviors in Mice
SP Hu, JJ Zhao, WX Wang, Y Liu, HF Wu, C Chen, L Yu, JB Gui
BioMed Research International 2014
Update zu Pharmakologie und Wirkung von Lokalanästhetika
J Ahrens, A Leffler
Der Anaesthesist 2014

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ISSN: 0021-9738 (print), 1558-8238 (online)

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