PIEZO2-dependent rapid pain system in humans and mice.

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Bouchatta, Otmane, Brodzki, Marek, Manouze, Houria, Carballo, Gabriela B, Kindström, Emma, de-Faria, Felipe M, Yu, Huasheng, Kao, Anika R, Thorell, Oumie, Liljencrantz, Jaquette et al (show 19 more authors) , Ng, Kevin KW, Frangos, Eleni, Ragnemalm, Bengt, Saade, Dimah, Bharucha-Goebel, Diana, Szczot, Ilona, Moore, Warren, Terejko, Katarzyna, Cole, Jonathan, Bonnemann, Carsten, Luo, Wenquin, Mahns, David A, Larsson, Max, Gerling, Gregory J, Marshall, Andrew G ORCID: 0000-0001-8273-7089, Chesler, Alexander T, Olausson, Håkan, Nagi, Saad S ORCID: 0000-0001-8773-8232 and Szczot, Marcin ORCID: 0000-0002-3902-059X (2023) PIEZO2-dependent rapid pain system in humans and mice. [Preprint]

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Abstract

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception - a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare Aβ deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on Aβ input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.

Item Type:	Preprint
Uncontrolled Keywords:	32 Biomedical and Clinical Sciences, 3209 Neurosciences, 3202 Clinical Sciences, Pain Research, Neurosciences, Clinical Research, Chronic Pain, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Neurological
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	26 Feb 2024 09:21
Last Modified:	23 May 2026 08:22
DOI:	10.1101/2023.12.01.569650
Open Access URL:	https://www.biorxiv.org/content/10.1101/2023.12.01...
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178861
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