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

Abstract

The brush of a feather or 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 show that optogenetic activation of Piezo2-expressing sensory neurons induces nociception in mice. Mice that lack Piezo2 in caudal sensory neurons have impaired nocifensive responses to mechanical stimuli. Consistently, Ex vivo recordings in skin-nerve preparations from these mice show diminished Aδ-nociceptor and C-fiber firing in response to mechanical stimulations. Punctate and dynamic allodynia in response to capsaicin-induced inflammation and spared nerve injury was absent in P iezo2-deficient mice. These results indicate that Piezo2 mediates inflammation- and nerve injury-induced sensitized mechanical pain, and suggest that targeting PIEZO2 might be an effective strategy for treating mechanical allodynia.

One Sentence Summary:

Piezo2 ion channels mediate mechanical allodynia in mice