An ultrafast system for signaling mechanical pain in human skin

Saad S Nagi; Andrew G Marshall; Adarsh Makdani; Ewa Jarocka; Jaquette Liljencrantz; Mikael Ridderström; Sumaiya Shaikh; Francis O'Neill; Dimah Saade; Sandra Donkervoort; A Reghan Foley; Jan Minde; Mats Trulsson; Jonathan Cole; Carsten G Bönnemann; Alexander T Chesler; M Catherine Bushnell; Francis McGlone; Håkan Olausson

doi:10.1126/sciadv.aaw1297

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An ultrafast system for signaling mechanical pain in human skin

Journal article

Open access

Peer reviewed

An ultrafast system for signaling mechanical pain in human skin

Saad S Nagi, Andrew G Marshall, Adarsh Makdani, Ewa Jarocka, Jaquette Liljencrantz, Mikael Ridderström, Sumaiya Shaikh, Francis O'Neill, Dimah Saade, Sandra Donkervoort, …

Science advances, Vol.5(7), pp.eaaw1297-eaaw1297

07/2019

DOI: 10.1126/sciadv.aaw1297

PMCID: PMC6609212

PMID: 31281886

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Abstract

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.

Signal Transduction

Adult

Aged

Aged, 80 and over

Axons - physiology

Electric Stimulation

Female

Hereditary Sensory and Autonomic Neuropathies - genetics

Hereditary Sensory and Autonomic Neuropathies - physiopathology

Humans

Ion Channels - genetics

Loss of Function Mutation

Male

Mechanoreceptors - metabolism

Mechanotransduction, Cellular - physiology

Middle Aged

Nerve Fibers, Myelinated - metabolism

Neurons, Afferent - metabolism

Neurophysiology - methods

Nociceptors - metabolism

Pain - metabolism

Skin - metabolism

Young Adult

Details

Title: Subtitle: An ultrafast system for signaling mechanical pain in human skin
Creators: Saad S Nagi - Western Sydney University
Andrew G Marshall - University of Manchester
Adarsh Makdani - Liverpool John Moores University
Ewa Jarocka - Umeå University
Jaquette Liljencrantz - University of Gothenburg
Mikael Ridderström - Umeå University
Sumaiya Shaikh - Linköping University
Francis O'Neill - University of Liverpool
Dimah Saade - National Institute of Neurological Disorders and Stroke
Sandra Donkervoort - National Institute of Neurological Disorders and Stroke
A Reghan Foley - National Institute of Neurological Disorders and Stroke
Jan Minde - Umeå University
Mats Trulsson - Karolinska Institutet
Jonathan Cole - Bournemouth University
Carsten G Bönnemann - National Institute of Neurological Disorders and Stroke
Alexander T Chesler - National Center for Complementary and Integrative Health
M Catherine Bushnell - National Center for Complementary and Integrative Health
Francis McGlone - University of Liverpool
Håkan Olausson - Linköping University Hospital
Resource Type: Journal article
Publication Details: Science advances, Vol.5(7), pp.eaaw1297-eaaw1297
DOI: 10.1126/sciadv.aaw1297
PMID: 31281886
PMCID: PMC6609212
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Grant note: DOI: 10.13039/501100000323, name: Pain Relief Foundation; DOI: 10.13039/501100000323, name: Pain Relief Foundation; DOI: 10.13039/501100000323, name: Pain Relief Foundation; DOI: 10.13039/501100001862, name: Swedish Research Council Formas; DOI: 10.13039/100000065, name: NINDS; name: ALF Region Östergötland; name: Intramural Research Program of the NIH, specifically the NCCIH; name: DDIR Innovation Award; name: Intramural Research Program of the NIH, specifically the NCCIH; name: ALF Region Östergötland
Language: English
Date published: 07/2019
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984354039602771

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