Journal Article

DZNE-2026-00304

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular architecture of human dermal sleeping nociceptors.

Körner, J. ; Howard, D. ; Solinski, H. J. ; Mancilla Moreno, M. ; Haag, N. ; Fiebig, A. ; Maxion, A. ; Bhuiyan, S. A. ; Toklucu, I. ; Bott, R. A. ; Sankaranarayanan, I. ; Tavares-Ferreira, D. ; Shiers, S. ; Inturi, N. N. ; Eberhardt, E. ; Ernst, L. ; Bonaguro, L.DZNE* ; Schulte-Schrepping, J.DZNE* ; Beyer, M. D.DZNE* ; Stiehl, T. ; Renthal, W. ; Kurth, I. ; Tigerholm, J. ; Serra, J. ; Price, T. J. ; Schmelz, M. ; Namer, B. ; Tripathy, S. ; Lampert, A.

2026
Cell Press [Cambridge, Mass.]

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Please use a persistent id in citations: doi:10.1016/j.cell.2025.12.048

Abstract: 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.

Keyword(s): Humans (MeSH) ; Nociceptors: metabolism (MeSH) ; Animals (MeSH) ; Skin: metabolism (MeSH) ; Skin: innervation (MeSH) ; Somatostatin: metabolism (MeSH) ; Somatostatin: genetics (MeSH) ; Male (MeSH) ; Nerve Fibers, Unmyelinated: metabolism (MeSH) ; Female (MeSH) ; Neuralgia: metabolism (MeSH) ; Sleep (MeSH) ; Transcriptome (MeSH) ; Adult (MeSH) ; Dermis: metabolism (MeSH) ; Nav1.9 ; OSMR ; Patch-seq ; dorsal root ganglion ; mechano-insensitive C-fibers ; microneurography ; neuropathic pain ; oncostatin M ; single-cell transcriptomics ; sleeping nociceptors ; Somatostatin

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Contributing Institute(s):

1. Molecular and Translational Immunaging (AG Bonaguro)
2. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
3. Immunogenomics and Neurodegeneration (AG Beyer)
4. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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