Molecular architecture of human dermal sleeping nociceptors
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.
Authors
- Hans Jürgen Solinski (ORCID: https://orcid.org/0000-0001-6606-3731)
- Anna Maxion (ORCID: https://orcid.org/0009-0001-7777-6478)
- Jannis Körner (ORCID: https://orcid.org/0000-0002-8537-1606)
- William Renthal (ORCID: https://orcid.org/0000-0003-0206-2101)
- Natja Haag (ORCID: https://orcid.org/0000-0002-2482-5969)
- Shamsuddin A. Bhuiyan (ORCID: https://orcid.org/0000-0003-3260-600X)
- Idil Toklucu (ORCID: https://orcid.org/0009-0005-4403-3028)
- Lisa Ernst (ORCID: https://orcid.org/0000-0003-3808-4222)
- Stephanie Shiers (ORCID: https://orcid.org/0000-0002-9646-1850)
- Raya Bott
- Thomas Stiehl (ORCID: https://orcid.org/0000-0001-9686-9197)
- Serra Jordi
- Shreejoy J. Tripathy (ORCID: https://orcid.org/0000-0002-1007-9061)
- Marisol Mancilla Moreno (ORCID: https://orcid.org/0000-0002-6479-4407)
- Martin Schmelz (ORCID: https://orcid.org/0000-0002-3536-8177)
- Andrea Fiebig
- Diana Tavares-Ferreira
- Ingo Kurth
- Derek Howard
- Jonas Schulte-Schrepping
- Ishwarya Sankaranarayanan
- Nikhil N. Inturi
- Esther Eberhardt
- Barbara Namer
- Marc D. Beyer
- Jenny Tigerholm
- Angelika Lampert
- Theodore J. Price
Institutions
- Brigham and Women's Hospital (US)
- Centre for Addiction and Mental Health (CA)
- Harvard University (US)
- The University of Texas at Dallas (US)
- Heidelberg University (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital Heidelberg (DE)
- Universitätsklinikum Aachen (DE)
- King's College Hospital (GB)
- University Medical Centre Mannheim (DE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Cell
- Published
- 2026-02-04
- DOI
- https://doi.org/10.1016/j.cell.2025.12.048
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00