An ultrafast system for signaling mechanical pain in human skin

Nagi, Saad, Marshall, Andrew ORCID: 0000-0001-8273-7089, Makdani, Adarsh, Jarocka, Ewa, Liljencrantz, Jaquette, Ridderström, Mikael, Shaikh, Sumaiya, O'Neill, FE ORCID: 0000-0002-6009-1026, Saade, Dimah, Donkervoort, Sandra
et al (show 9 more authors) (2019) An ultrafast system for signaling mechanical pain in human skin. Science Advances, 5 (07).

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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.

Item Type: Article
Uncontrolled Keywords: Axons, Nerve Fibers, Myelinated, Neurons, Afferent, Mechanoreceptors, Nociceptors, Skin, Humans, Hereditary Sensory and Autonomic Neuropathies, Pain, Ion Channels, Electric Stimulation, Neurophysiology, Signal Transduction, Mechanotransduction, Cellular, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Loss of Function Mutation
Depositing User: Symplectic Admin
Date Deposited: 04 Jul 2019 14:25
Last Modified: 04 Feb 2023 08:21
DOI: 10.1126/sciadv.aaw1297
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