PIEZO2 mediates injury-induced tactile pain in mice and humans

Marcin Szczot; Jaquette Liljencrantz; Nima Ghitani; Arnab Barik; Ruby Lam; James H Thompson; Diana Bharucha-Goebel; Dimah Saade; Aaron Necaise; Sandra Donkervoort; A Reghan Foley; Taylor Gordon; Laura Case; M Catherine Bushnell; Carsten G Bönnemann; Alexander T Chesler

doi:10.1126/scitranslmed.aat9892

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PIEZO2 mediates injury-induced tactile pain in mice and humans

Journal article

Open access

Peer reviewed

PIEZO2 mediates injury-induced tactile pain in mice and humans

Marcin Szczot, Jaquette Liljencrantz, Nima Ghitani, Arnab Barik, Ruby Lam, James H Thompson, Diana Bharucha-Goebel, Dimah Saade, Aaron Necaise, Sandra Donkervoort, …

Science translational medicine, Vol.10(462), eaat9892

10/10/2018

DOI: 10.1126/scitranslmed.aat9892

PMCID: PMC6875774

PMID: 30305456

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Abstract

Tissue injury and inflammation markedly alter touch perception, making normally innocuous sensations become intensely painful. Although this sensory distortion, known as tactile allodynia, is one of the most common types of pain, the mechanism by which gentle mechanical stimulation becomes unpleasant remains enigmatic. The stretch-gated ion channel PIEZO2 has been shown to mediate light touch, vibration detection, and proprioception. However, the role of this ion channel in nociception and pain has not been resolved. Here, we examined the importance of Piezo2 in the cellular representation of mechanosensation using in vivo imaging in mice. Piezo2-knockout neurons were completely insensitive to gentle dynamic touch but still responded robustly to noxious pinch. During inflammation and after injury, Piezo2 remained essential for detection of gentle mechanical stimuli. We hypothesized that loss of PIEZO2 might eliminate tactile allodynia in humans. Our results show that individuals with loss-of-function mutations in PIEZO2 completely failed to develop sensitization and painful reactions to touch after skin inflammation. These findings provide insight into the basis for tactile allodynia, identify the PIEZO2 mechanoreceptor as an essential mediator of touch under inflammatory conditions, and suggest that this ion channel might be targeted for treating tactile allodynia.

Animals

Capsaicin - pharmacology

Chronic Disease

Disease Models, Animal

Humans

Hyperalgesia - pathology

Imaging, Three-Dimensional

Inflammation - complications

Inflammation - pathology

Ion Channels - genetics

Ion Channels - metabolism

Mice, Inbred C57BL

Mice, Knockout

Mutation - genetics

Neurons - metabolism

Pain - complications

Pain - genetics

Pain - metabolism

Recombination, Genetic - genetics

Touch

Details

Title: Subtitle: PIEZO2 mediates injury-induced tactile pain in mice and humans
Creators: Marcin Szczot - National Center for Complementary and Integrative Health
Jaquette Liljencrantz - National Center for Complementary and Integrative Health
Nima Ghitani - National Center for Complementary and Integrative Health
Arnab Barik - National Center for Complementary and Integrative Health
Ruby Lam - National Center for Complementary and Integrative Health
James H Thompson - National Center for Complementary and Integrative Health
Diana Bharucha-Goebel - Children's National
Dimah Saade - National Institute of Neurological Disorders and Stroke
Aaron Necaise - National Center for Complementary and Integrative Health
Sandra Donkervoort - National Institute of Neurological Disorders and Stroke
A Reghan Foley - National Institute of Neurological Disorders and Stroke
Taylor Gordon - National Center for Complementary and Integrative Health
Laura Case - National Center for Complementary and Integrative Health
M Catherine Bushnell - National Center for Complementary and Integrative Health
Carsten G Bönnemann - National Institute of Neurological Disorders and Stroke
Alexander T Chesler - National Center for Complementary and Integrative Health
Resource Type: Journal article
Publication Details: Science translational medicine, Vol.10(462), eaat9892
DOI: 10.1126/scitranslmed.aat9892
PMID: 30305456
PMCID: PMC6875774
NLM abbreviation: Sci Transl Med
ISSN: 1946-6234
eISSN: 1946-6242
Grant note: ZIA AT000028-05 / Intramural NIH HHS
Language: English
Date published: 10/10/2018
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984353835702771

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