P1.02. PIEZO2-DEPENDENT RAPID PAIN SYSTEM IN HUMANS AND MICE
Marek Brodzki1, Otmane Bouchatta1, Houria Manouze1, Gabriela B. Carballo1, Huasheng Yu2, Emma Kindström1, Felipe M. de- Faria1, Oumie Thorell1,3, Jaquette Liljencrantz4,5, Christoffer Karlsson1, Melisa B. Maidana Capitán1, Kevin K. W. Ng1, Katarzyna Terejko1,6, Max Larsson1, Wenqin Luo2, Andrew G. Marshall1,7, Alexander T. Chesler4,8, Håkan Olausson1, Saad S. Nagi1,3, Marcin Szczot1
1 Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden
2 Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
3 School of Medicine, Western Sydney University, Sydney, Australia
4 National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, USA
5 Department of Anesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
6 Łukasiewicz Research Network - PORT Polish Center for Technology Development, Wroclaw, Poland
7 Institute of Life Course and Medical Sciences, University of Liverpool, UK
8 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA
INTRODUCTION: Mechanical pain in humans manifests in diverse forms, yet current knowledge of cutaneous nociceptor classes does not fully explain this variety. One sensation that is particularly understudied is the pain evoked by hair pulling.
AIM(S): To identify and characterize the neural mechanisms underlying hair-pull pain in humans and determine the role of PIEZO2 and specific nociceptor types in this process.
METHOD(S): We studied individuals with PIEZO2 deficiency syndrome psychophysically, performed single-unit axonal recordings, pharmacological mapping, and anatomical tracing. Functional and anatomical imaging in mice as well as behavioral studies in humans, including Aβ-deafferented individuals and nerve block experiments, were also conducted.
RESULTS: Hair-pull pain was absent in PIEZO2-deficient individuals, indicating its dependence on PIEZO2. Nerve recordings identified a class of rapidly conducting, cooling-sensitive nociceptors selectively responsive to hair-pull stimuli. These were pharmacologically linked to a distinct transcriptomic class and shown to be myelinated and associated with hair follicles. In mice, Piezo2 was essential for robust activation of homologous nociceptors. In humans, hair-pull stimuli triggered a unique nocifensive response and required Aβ-fiber input for pain perception.
CONCLUSIONS: We reveal a previously unrecognized class of human nociceptors specialized for hair-pull pain, defined by distinct molecular, anatomical, and functional properties, and dependent on PIEZO2 and Aβ-fiber signaling.
FINANCIAL SUPPORT: Swedish Research Council Starting Grant no. 2020-01107; Knut and Alice Wallenberg Foundation Fellowship; Swedish Research Council Project Grant no. 2021-03054; Knut and Alice Wallenberg Project Grant no. 2019.0047; Knut and Alice Wallenberg Clinical Scholar Grant no. 2019.0487; ALF Grants Region Östergötland; Swedish Society of Medicine Project Grant; Magnus Bergvalls Stiftelse Research Grant; Western Sydney University Funding Scheme; Intramural Research Program of the NIH, specifically the NCCIH