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

Item Type:Article
Title:The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice
Creators Name:Murthy, S.E. and Loud, M.C. and Daou, I. and Marshall, K.L. and Schwaller, F. and Kühnemund, J. and Francisco, A.G. and Keenan, W.T. and Dubin, A.E. and Lewin, G.R. and Patapoutian, A.
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 Aδ-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.
Source:Science Translational Medicine
ISSN:1946-6234
Publisher:American Association for the Advancement of Science (U.S.A.)
Volume:10
Number:462
Page Range:eaat9897
Date:10 October 2018
Official Publication:https://doi.org/10.1126/scitranslmed.aat9897
PubMed:View item in PubMed

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