Researchers from the Centre for Addiction and Mental Health (CAMH) in Canada and the Institute of Neurophysiology at Uniklinik RWTH Aachen in Germany have identified the molecular signature of "sleeping nociceptors," a type of nerve cell involved in chronic pain. The study, set to be published in Cell on February 4, 2026, addresses a long-standing gap in pain research by linking the electrical behavior of these neurons with their genetic profile.
Sleeping nociceptors are nerve cells that usually remain inactive but can become overactive, contributing to chronic neuropathic pain—a condition affecting about ten percent of people worldwide. Previously, researchers could distinguish these cells based on their electrical properties but did not know which genes were active within them. This lack of genetic information made it difficult to develop targeted therapies.
The international team was led by Univ.-Prof. Dr. Angelika Lampert from Uniklinik RWTH Aachen and Dr. Shreejoy Tripathy from CAMH and the University of Toronto. Using Patch-Seq, a technique that measures both electrophysiological activity and gene expression in single cells, co-first author Dr. Jannis Körner recorded data from individual neurons. Derek Howard, also a co-first author and CAMH Research Methods Specialist under Dr. Tripathy's supervision, led bioinformatics analyses that integrated these findings.
This collaboration enabled researchers to match specific genes with sleeping nociceptors' unique electrical characteristics—a process described as providing a "Rosetta stone" for pain research.
Their results show that sleeping nociceptors have a distinct molecular profile featuring markers such as the oncostatin M receptor (OSMR) and neuropeptide somatostatin (SST). Dr. Körner said: "The findings also point to additional drug targets, including the ion channel Nav1.9, which was highly expressed in sleeping nociceptors and contributes to their distinctive electrical properties." He added: "Put simply, this channel likely helps control how easily sleeping nociceptors become active and targeting Nav1.9 may enable the development of medications that selectively quiet these pain-causing neurons."
Derek Howard noted: "Our bioinformatics analyses pointed to OSMR as a marker of sleeping nociceptors, but that's just a prediction until someone tests it. What made this collaboration special was our colleagues' willingness to take that prediction and validate it." Dr. Körner explained: "In our final set of psychophysics experiments, we showed that oncostatin M, which activates OSMR, specifically modulates sleeping nociceptors in the human skin. This confirmed our molecular predictions directly in humans."
Prof. Lampert emphasized interdisciplinary cooperation: "This work demonstrates the power of interdisciplinary and international cooperation. The success of the study relies on the close integration of specialized centers: while the key experiments were performed in Aachen, crucial single-cell and spatial transcriptomic efforts were undertaken in Mannheim and Dallas." Dr. Tripathy commented: "It was a privilege to be part of such an 'all-star' team of experts. This project is a testament to what can be achieved when we combine diverse scientific perspectives to solve a common problem."
Additional contributions came from researchers at institutions including King's College London; Heidelberg University; University of Würzburg; University of Texas at Dallas; Harvard University; and others.
