Sleeping Nociceptors: Molecular Signature of Chronic Pain Identified

Researchers have identified a unique molecular signature for “sleeping nociceptors,” a type of pain-sensing nerve cell that remains dormant unless triggered into action, potentially offering new avenues for treating chronic neuropathic pain. The findings, published today, February 4, 2026, in the journal Cell, detail the genetic characteristics of these neurons and pinpoint potential targets for future pain therapies.

Approximately 10% of the global population experiences neuropathic pain, a condition often linked to the abnormal activity of these sleeping nociceptors. Unlike typical pain signals that arise from an immediate injury, neuropathic pain can persist even without an obvious external trigger. These neurons, while known to contribute to chronic pain, have remained elusive at the molecular level – until now.

An international team led by Univ.-Prof. Dr. Angelika Lampert of Uniklinik RWTH Aachen in Germany, and Dr. Shreejoy Tripathy of the Centre for Addiction and Mental Health (CAMH) in Canada, successfully bridged the gap between the electrical behavior and genetic activity of individual neurons. By combining electrophysiology with single-cell genetic sequencing, they were able to define the specific genes that characterize sleeping nociceptors.

This collaborative effort resulted in what researchers are calling a “Rosetta stone” for pain research – a method for translating between the distinct fields of nerve cell electricity and genetics. This translation allows for a clearer understanding of how these neurons function and, crucially, how they might be targeted with new treatments.

Molecular Hallmarks of Sleeping Nociceptors

The research team’s analysis revealed a specific molecular signature defining sleeping nociceptors, notably including the oncostatin M receptor (OSMR) and the neuropeptide somatostatin (SST). Dr. Jannis Körner, a clinician-scientist at Uniklinik, explained that the findings also highlight additional potential drug targets, including the ion channel Nav1.9, which is highly expressed in these neurons and contributes to their unique electrical properties. Targeting Nav1.9 could potentially allow for the development of medications that selectively quiet these pain-causing neurons.

Derek Howard, a Research Methods Specialist at CAMH, added that bioinformatics analyses initially pointed to OSMR as a key marker for sleeping nociceptors. However, validation was crucial. “What made this collaboration special was our colleagues’ willingness to take that prediction and validate it,” he said. Researchers confirmed their molecular predictions directly in human skin by demonstrating that oncostatin M, which activates OSMR, specifically modulates sleeping nociceptors.

“Our work establishes a new conceptual framework for understanding the emergence of neuropathic pain at the molecular level, while at the same time opening concrete perspectives for the development of new, targeted therapies.”

Dr. Angelika Lampert, Director of the Institute of Neurophysiology at Uniklinik RWTH Aachen, Germany

The study identified that sleeping nociceptors are a distinct class of sensory neurons that can become spontaneously active, causing persistent pain even without an evident stimulus. These neurons represent a significant component of the neuropathic pain experienced by approximately 20% of American adults.

A Multi-Disciplinary International Effort

Prof. Lampert emphasized the importance of the collaborative nature of the research. “This work demonstrates the power of interdisciplinary and international cooperation,” she stated. “The success of the study relies on the close integration of specialized centers.” Key experiments were performed in Aachen, while crucial single-cell and spatial transcriptomic efforts were undertaken in Mannheim and Dallas.

Dr. Tripathy added, “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.”

The research team also included contributions from researchers led by Barbara Namer (University of Würzburg), Jordi Serra (King’s College London), Martin Schmelz and Hans-Jürgen Solinski (Heidelberg University), Ted Price (University of Texas, Dallas), and William Renthal (Harvard University).

The cell bodies of these sleeping nociceptors are located in the dorsal root ganglia, nerve cells clustered near the base of the spine that relay sensory signals from the peripheral nervous system to the central nervous system.