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)
(2023)
PIEZO2-dependent rapid pain system in humans and mice.
[Preprint]
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 |
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Uncontrolled Keywords: | Neurosciences, Pain Research, Chronic Pain, 1.1 Normal biological development and functioning, 1 Underpinning research, Neurological |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 26 Feb 2024 09:21 |
Last Modified: | 27 Apr 2024 22:53 |
DOI: | 10.1101/2023.12.01.569650 |
Open Access URL: | https://www.biorxiv.org/content/10.1101/2023.12.01... |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178861 |