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The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach
BACKGROUND: Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fiber...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966804/ https://www.ncbi.nlm.nih.gov/pubmed/31952468 http://dx.doi.org/10.1186/s12967-019-02200-2 |
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author | Rosenberger, Daniela C. Binzen, Uta Treede, Rolf-Detlef Greffrath, Wolfgang |
author_facet | Rosenberger, Daniela C. Binzen, Uta Treede, Rolf-Detlef Greffrath, Wolfgang |
author_sort | Rosenberger, Daniela C. |
collection | PubMed |
description | BACKGROUND: Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fibers. Exploring contribution of candidate signal transduction mechanisms to heat pain in humans needs translational models. METHODS: We used focused, non-damaging, short near-infrared laser heat stimuli (wavelength 1470/1475 nm) to study the involvement of TRPV1-expressing nerve fibers in the encoding of heat pain intensity. Human psychophysics (both sexes) were compared to calcium transients in native rat DRG neurons and heterologously expressing HEK293 cells. RESULTS: Heating of dermal and epidermal nerve fibers in humans with laser stimuli of ≥ 2.5 mJ (≥ 25 ms, 100 mW) induced pain that increased linearly as a function of stimulus intensity in double logarithmic space across two orders of magnitude and was completely abolished by desensitization using topical capsaicin. In DRG neurons and TRPV1-expressing HEK cells, heat sensitivity was restricted to capsaicin sensitive cells. Strength duration curves (2–10 ms range) and thresholds (DRGs 0.56 mJ, HEK cells 0.52 mJ) were nearly identical. Tachyphylaxis upon repetitive stimulation occurred in HEK cells (54%), DRGs (59%), and humans (25%). CONCLUSION: TRPV1-expressing nociceptors encode transient non-damaging heat pain in humans, thermal gating of TRPV1 is similar in HEK cells and DRG neurons, and TRPV1 tachyphylaxis is an important modulator of heat pain sensitivity. These findings suggest that TRPV1 expressed in dermal and epidermal populations of nociceptors serves as first line defense against heat injury. |
format | Online Article Text |
id | pubmed-6966804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69668042020-01-22 The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach Rosenberger, Daniela C. Binzen, Uta Treede, Rolf-Detlef Greffrath, Wolfgang J Transl Med Research BACKGROUND: Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fibers. Exploring contribution of candidate signal transduction mechanisms to heat pain in humans needs translational models. METHODS: We used focused, non-damaging, short near-infrared laser heat stimuli (wavelength 1470/1475 nm) to study the involvement of TRPV1-expressing nerve fibers in the encoding of heat pain intensity. Human psychophysics (both sexes) were compared to calcium transients in native rat DRG neurons and heterologously expressing HEK293 cells. RESULTS: Heating of dermal and epidermal nerve fibers in humans with laser stimuli of ≥ 2.5 mJ (≥ 25 ms, 100 mW) induced pain that increased linearly as a function of stimulus intensity in double logarithmic space across two orders of magnitude and was completely abolished by desensitization using topical capsaicin. In DRG neurons and TRPV1-expressing HEK cells, heat sensitivity was restricted to capsaicin sensitive cells. Strength duration curves (2–10 ms range) and thresholds (DRGs 0.56 mJ, HEK cells 0.52 mJ) were nearly identical. Tachyphylaxis upon repetitive stimulation occurred in HEK cells (54%), DRGs (59%), and humans (25%). CONCLUSION: TRPV1-expressing nociceptors encode transient non-damaging heat pain in humans, thermal gating of TRPV1 is similar in HEK cells and DRG neurons, and TRPV1 tachyphylaxis is an important modulator of heat pain sensitivity. These findings suggest that TRPV1 expressed in dermal and epidermal populations of nociceptors serves as first line defense against heat injury. BioMed Central 2020-01-17 /pmc/articles/PMC6966804/ /pubmed/31952468 http://dx.doi.org/10.1186/s12967-019-02200-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Rosenberger, Daniela C. Binzen, Uta Treede, Rolf-Detlef Greffrath, Wolfgang The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title | The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title_full | The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title_fullStr | The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title_full_unstemmed | The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title_short | The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach |
title_sort | capsaicin receptor trpv1 is the first line defense protecting from acute non damaging heat: a translational approach |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966804/ https://www.ncbi.nlm.nih.gov/pubmed/31952468 http://dx.doi.org/10.1186/s12967-019-02200-2 |
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