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The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons.
J Clin Invest. 2008 Feb; 118(2):763-76.JCI

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+Show Affiliations

Department of Anesthesiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18172555

Citation

Leffler, Andreas, et al. "The Vanilloid Receptor TRPV1 Is Activated and Sensitized By Local Anesthetics in Rodent Sensory Neurons." The Journal of Clinical Investigation, vol. 118, no. 2, 2008, pp. 763-76.
Leffler A, Fischer MJ, Rehner D, et al. The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. J Clin Invest. 2008;118(2):763-76.
Leffler, A., Fischer, M. J., Rehner, D., Kienel, S., Kistner, K., Sauer, S. K., Gavva, N. R., Reeh, P. W., & Nau, C. (2008). The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. The Journal of Clinical Investigation, 118(2), 763-76. https://doi.org/10.1172/JCI32751
Leffler A, et al. The Vanilloid Receptor TRPV1 Is Activated and Sensitized By Local Anesthetics in Rodent Sensory Neurons. J Clin Invest. 2008;118(2):763-76. PubMed PMID: 18172555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. AU - Leffler,Andreas, AU - Fischer,Michael J, AU - Rehner,Dietlinde, AU - Kienel,Stephanie, AU - Kistner,Katrin, AU - Sauer,Susanne K, AU - Gavva,Narender R, AU - Reeh,Peter W, AU - Nau,Carla, PY - 2007/05/21/received PY - 2007/11/07/accepted PY - 2008/1/4/pubmed PY - 2008/3/28/medline PY - 2008/1/4/entrez SP - 763 EP - 76 JF - The Journal of clinical investigation JO - J Clin Invest VL - 118 IS - 2 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/18172555/The_vanilloid_receptor_TRPV1_is_activated_and_sensitized_by_local_anesthetics_in_rodent_sensory_neurons_ L2 - https://doi.org/10.1172/JCI32751 DB - PRIME DP - Unbound Medicine ER -