Molecular architecture of human dermal sleeping nociceptors
Summary
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
Content
# Molecular architecture of human dermal sleeping nociceptors
*Published: 2026 Mar 19*
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.
DOI: 10.1016/j.cell.2025.12.048