The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice

Swetha E. Murthy, Meaghan C. Loud, Ihab Daou, Kara L. Marshall, Frederick Schwaller, Johannes Kühnemund, Allain G. Francisco, William T. Keenan, Adrienne E. Dubin, Gary R. Lewin, Ardem Patapoutian

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury can disrupt this sensory coding and result in maladaptive pain states, including mechanical allodynia, the development of pain in response to innocuous touch. However, the molecular mechanisms underlying the alteration of mechanical sensitization are poorly understood. In mice and humans, loss of mechanically activated PIEZO2 channels results in the inability to sense discriminative touch. However, the role of Piezo2 in acute and sensitized mechanical pain is not well defined. Here, we showed that optogenetic activation of Piezo2-expressing sensory neurons induced nociception in mice. Mice lacking Piezo2 in caudal sensory neurons had impaired nocifensive responses to mechanical stimuli. Consistently, ex vivo recordings in skin-nerve preparations from these mice showed diminished Ad-nociceptor and C-fiber firing in response to mechanical stimulation. Punctate and dynamic allodynia in response to capsaicin-induced inflammation and spared nerve injury was absent in Piezo2-deficient mice. These results indicate that Piezo2 mediates inflammationand nerve injury-induced sensitized mechanical pain, and suggest that targeting PIEZO2 might be an effective strategy for treating mechanical allodynia.

Original languageEnglish (US)
Article numbereaat9897
JournalScience translational medicine
Volume10
Issue number462
DOIs
StatePublished - Oct 10 2018
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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