Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans

Laura K. Case, Jaquette Liljencrantz, Nicholas Madian, Aaron Necaise, Justin Tubbs, Micaela McCall, Megan L. Bradson, Marcin Szczot, Mark H. Pitcher, Nima Ghitani, Eleni Frangos, Jonathan Cole, Diana Bharucha-Goebel, Dimah Saade, Tracy Ogata, Sandra Donkervoort, A. Reghan Foley, Carsten G. Bönnemann, Håkan Olausson, M. Catherine Bushnell () and Alexander T. Chesler ()
Additional contact information
Laura K. Case: National Center for Complementary and Integrative Health, NIH
Jaquette Liljencrantz: National Center for Complementary and Integrative Health, NIH
Nicholas Madian: National Center for Complementary and Integrative Health, NIH
Aaron Necaise: National Center for Complementary and Integrative Health, NIH
Justin Tubbs: National Center for Complementary and Integrative Health, NIH
Micaela McCall: National Center for Complementary and Integrative Health, NIH
Megan L. Bradson: National Center for Complementary and Integrative Health, NIH
Marcin Szczot: National Center for Complementary and Integrative Health, NIH
Mark H. Pitcher: National Center for Complementary and Integrative Health, NIH
Nima Ghitani: National Center for Complementary and Integrative Health, NIH
Eleni Frangos: National Center for Complementary and Integrative Health, NIH
Jonathan Cole: Bournemouth University
Diana Bharucha-Goebel: National Institutes of Health
Dimah Saade: National Institutes of Health
Tracy Ogata: National Institutes of Health
Sandra Donkervoort: National Institutes of Health
A. Reghan Foley: National Institutes of Health
Carsten G. Bönnemann: National Institutes of Health
Håkan Olausson: Linköping University
M. Catherine Bushnell: National Center for Complementary and Integrative Health, NIH
Alexander T. Chesler: National Center for Complementary and Integrative Health, NIH

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aβ fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aβ afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.

Date: 2021
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DOI: 10.1038/s41467-021-20939-5

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