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Molecular architecture of human dermal sleeping nociceptors.

Cell

Authors: Jannis Körner, Derek Howard, Hans Jürgen Solinski, Marisol Mancilla Moreno, Natja Haag, Andrea Fiebig, Anna Maxion, Shamsuddin A Bhuiyan, Idil Toklucu, Raya A Bott, Ishwarya Sankaranarayanan, Diana Tavares-Ferreira, Stephanie Shiers, Nikhil N Inturi, Esther Eberhardt, Lisa Ernst, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Marc D Beyer, Thomas Stiehl, William Renthal, Ingo Kurth, Jenny Tigerholm, Jordi Serra, Theodore J Price, Martin Schmelz, Barbara Namer, Shreejoy Tripathy, Angelika Lampert

Human dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. Using a Patch-seq approach, we combined single-cell transcriptomics, following electrophysiological characterization, with single-nucleus and spatial transcriptomics from pigs and integrated our findings with cross-species and human transcriptomic data. We functionally identified CMis in pig sensory neurons with patch clamp, using adapted protocols from human microneurography. We identified oncostatin M receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin M, the ligand of OSMR, exclusively modulates CMis. Our findings characterize the molecular architecture of human dermal sleeping nociceptors, providing a framework for mechanistic insight into neuropathic pain and potential therapeutic strategies.

Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

PMID: 41643676

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