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An ultrafast system for signaling mechanical pain in human skin.

Nagi, S.S., Marshall, A.G., Makdani, A., Jarocka, E., Liljencrantz, J., Ridderström, M., Shaikh, S., O'Neill, F., Saade, D., Donkervoort, S., Foley, A.R., Minde, J., Trulsson, M., Cole, J., Bönnemann, C.G., Chesler, A.T., Bushnell, M.C., McGlone, F. and Olausson, H., 2019. An ultrafast system for signaling mechanical pain in human skin. Science Advances, 5 (7), eaaw1297.

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eaaw1297.full.pdf - Published Version
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DOI: 10.1126/sciadv.aaw1297


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:Adult ; Aged ; Aged, 80 and over ; Axons ; Electric Stimulation ; Female ; Hereditary Sensory and Autonomic Neuropathies ; Humans ; Ion Channels ; Loss of Function Mutation ; Male ; Mechanoreceptors ; Mechanotransduction, Cellular ; Middle Aged ; Nerve Fibers, Myelinated ; Neurons, Afferent ; Neurophysiology ; Nociceptors ; Pain ; Signal Transduction ; Skin ; Young Adult
Group:Faculty of Health & Social Sciences
ID Code:35176
Deposited By: Symplectic RT2
Deposited On:09 Feb 2021 10:55
Last Modified:14 Mar 2022 14:26


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