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An ultrafast system for signaling mechanical pain in human skin
The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nocicep...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609212/ https://www.ncbi.nlm.nih.gov/pubmed/31281886 http://dx.doi.org/10.1126/sciadv.aaw1297 |
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author | Nagi, Saad S. Marshall, Andrew G. Makdani, Adarsh Jarocka, Ewa Liljencrantz, Jaquette Ridderström, Mikael Shaikh, Sumaiya O’Neill, Francis Saade, Dimah Donkervoort, Sandra Foley, A. Reghan Minde, Jan Trulsson, Mats Cole, Jonathan Bönnemann, Carsten G. Chesler, Alexander T. Bushnell, M. Catherine McGlone, Francis Olausson, Håkan |
author_facet | Nagi, Saad S. Marshall, Andrew G. Makdani, Adarsh Jarocka, Ewa Liljencrantz, Jaquette Ridderström, Mikael Shaikh, Sumaiya O’Neill, Francis Saade, Dimah Donkervoort, Sandra Foley, A. Reghan Minde, Jan Trulsson, Mats Cole, Jonathan Bönnemann, Carsten G. Chesler, Alexander T. Bushnell, M. Catherine McGlone, Francis Olausson, Håkan |
author_sort | Nagi, Saad S. |
collection | PubMed |
description | The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents. |
format | Online Article Text |
id | pubmed-6609212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66092122019-07-05 An ultrafast system for signaling mechanical pain in human skin Nagi, Saad S. Marshall, Andrew G. Makdani, Adarsh Jarocka, Ewa Liljencrantz, Jaquette Ridderström, Mikael Shaikh, Sumaiya O’Neill, Francis Saade, Dimah Donkervoort, Sandra Foley, A. Reghan Minde, Jan Trulsson, Mats Cole, Jonathan Bönnemann, Carsten G. Chesler, Alexander T. Bushnell, M. Catherine McGlone, Francis Olausson, Håkan Sci Adv Research Articles The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents. American Association for the Advancement of Science 2019-07-03 /pmc/articles/PMC6609212/ /pubmed/31281886 http://dx.doi.org/10.1126/sciadv.aaw1297 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Nagi, Saad S. Marshall, Andrew G. Makdani, Adarsh Jarocka, Ewa Liljencrantz, Jaquette Ridderström, Mikael Shaikh, Sumaiya O’Neill, Francis Saade, Dimah Donkervoort, Sandra Foley, A. Reghan Minde, Jan Trulsson, Mats Cole, Jonathan Bönnemann, Carsten G. Chesler, Alexander T. Bushnell, M. Catherine McGlone, Francis Olausson, Håkan An ultrafast system for signaling mechanical pain in human skin |
title | An ultrafast system for signaling mechanical pain in human skin |
title_full | An ultrafast system for signaling mechanical pain in human skin |
title_fullStr | An ultrafast system for signaling mechanical pain in human skin |
title_full_unstemmed | An ultrafast system for signaling mechanical pain in human skin |
title_short | An ultrafast system for signaling mechanical pain in human skin |
title_sort | ultrafast system for signaling mechanical pain in human skin |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609212/ https://www.ncbi.nlm.nih.gov/pubmed/31281886 http://dx.doi.org/10.1126/sciadv.aaw1297 |
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