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Sci Transl Med. 2018 Oct 10;10(462). pii: eaat9892. doi: 10.1126/scitranslmed.aat9892.

PIEZO2 mediates injury-induced tactile pain in mice and humans.

Author information

1
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA.
2
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
3
Department of Neurology, Children's National Medical Center, Washington, DC 20010, USA.
4
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA. alexander.chesler@nih.gov.

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.

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