In a groundbreaking study set to be published in the prestigious journal Cell on February 4, 2026, researchers from the Centre for Addiction and Mental Health (CAMH) in Canada and the Institute of Neurophysiology at Uniklinik RWTH Aachen in Germany have unraveled the molecular underpinnings of a mysterious class of pain-sensing neurons known as “sleeping nociceptors.” These neurons, which usually remain dormant and unresponsive to external stimuli like touch or pressure, have long been implicated in chronic neuropathic pain states when they aberrantly activate. This research not only identifies the genetic profile of these elusive cells but also paves the way for targeted therapies to alleviate debilitating chronic pain conditions.
Neuropathic pain affects approximately 10% of the global population—manifesting as persistent, often unbearable pain without any obvious injury or external trigger. A major obstacle in treating this condition has been the incomplete understanding of the exact biological mechanisms driving the spontaneous activity of sleeping nociceptors. Although electrophysiological studies have previously described their functional properties, the genes responsible for their unique behavior remained unknown, creating a significant barrier to the development of effective, precision-targeted drugs.
Led by Univ.-Prof. Dr. Angelika Lampert from Uniklinik RWTH Aachen and Dr. Shreejoy Tripathy from CAMH and the University of Toronto, the international research team adopted an innovative multidisciplinary approach combining electrophysiology and cutting-edge single-cell genetic sequencing techniques. They employed Patch-Seq, an advanced technology that enables simultaneous recordings of the neurons’ electrical activity and detailed analysis of their gene expression. This integrative methodology allowed for an unprecedented molecular characterization of individual sleeping nociceptors.
Dr. Jannis Körner, a clinician-scientist central to the study, meticulously gathered electrophysiological data from these neurons, capturing how they respond or remain silent under various conditions. Concurrently, co-first author Derek Howard, a bioinformatics specialist, performed sophisticated computational analyses to decode the complex gene expression patterns that distinguish sleeping nociceptors from other sensory neurons. Their combined efforts deciphered what can be regarded as a “Rosetta stone” for pain research, connecting previously disparate domains of neurophysiology and molecular genetics.
The researchers discovered that sleeping nociceptors exhibit a specific molecular signature, defining their identity and functional characteristics. Central to this signature are the oncostatin M receptor (OSMR) and the neuropeptide somatostatin (SST), both of which are critically involved in modulating neuronal excitability and pain signaling pathways. Notably, the ion channel Nav1.9 emerged as a key player; it showed high expression levels in sleeping nociceptors and appeared to regulate their electrical properties, effectively controlling their transition from a quiet to an active state.
Targeting Nav1.9 presents a compelling therapeutic opportunity because this ion channel selectively affects sleeping nociceptors, potentially enabling the development of drugs that silence only the pain-causing neurons without interfering with normal sensory functions. Dr. Körner emphasized that understanding Nav1.9’s role could revolutionize chronic pain treatment by offering medications with fewer side effects and higher specificity compared to current analgesics.
Further validation of the molecular findings was achieved through psychophysical experiments conducted on human skin, where oncostatin M—the ligand for OSMR—was shown to specifically modulate the activity of sleeping nociceptors. This critical translational step confirmed that the molecular signals identified in lab models are directly relevant in human biology, strengthening the evidence base for therapeutic targeting of these pathways.
The collaborative effort behind this study exemplifies the power of interdisciplinary and international scientific cooperation. Prof. Lampert highlighted that the project’s success relied on integrating expertise from multiple specialized centers across Germany, Canada, the UK, and the USA. From single-cell transcriptomics to spatial gene expression mapping, the convergence of diverse technologies and perspectives enabled breakthroughs that would have been unattainable in isolation.
Contributing groups included leading pain researchers such as Barbara Namer from the University of Würzburg, Jordi Serra at King’s College London, Martin Schmelz and Hans-Jürgen Solinski from Heidelberg University, Ted Price at the University of Texas, Dallas, and William Renthal at Harvard University, underscoring the global scale and multidisciplinary nature of the project. Their combined expertise spanned neurophysiology, molecular biology, computational science, and clinical medicine, reflecting a comprehensive approach to unraveling chronic pain mechanisms.
This study marks a transformative advance in our understanding of neuropathic pain at the molecular level, establishing a new conceptual framework that links cellular electrophysiology with genomics. Beyond sheer discovery, it opens tangible avenues for drug development focused on silencing the rogue activity of sleeping nociceptors, which could dramatically improve quality of life for millions suffering from chronic pain worldwide.
With chronic pain posing a substantial burden on healthcare systems globally, innovations such as these not only hold promise for novel analgesics but also illuminate broader principles applicable to other sensory and neurological disorders. By bridging the gap between basic neuroscience research and clinical application, the study exemplifies how targeted molecular therapies can emerge from integrative, data-driven exploration of cell identity.
Moving forward, the researchers plan to deepen their investigation into the precise mechanisms by which OSMR activation influences nociceptor activity and how Nav1.9 gating contributes to pain sensitization. Moreover, clinical trials testing pharmacological modulation of these targets could catalyze the next generation of chronic pain treatments, moving beyond symptomatic relief toward mechanistic intervention.
The discovery of a comprehensive molecular signature for sleeping nociceptors thus constitutes a landmark achievement—transforming a long-standing mystery in pain research into a clear target for precision medicine. This work heralds an exciting era where the silent culprits of chronic pain can finally be identified, understood, and rendered silent once more.
Subject of Research: People
Article Title: Molecular architecture of human dermal sleeping nociceptors
News Publication Date: 4-Feb-2026
Web References:
https://dx.doi.org/10.1016/j.cell.2025.12.048
Keywords:
Sensory receptors, Pain, Neurophysiology, Chronic pain, Neuropathic pain, Nociceptors, Molecular genetics, Electrophysiology, Ion channels, Nav1.9, Oncostatin M receptor (OSMR), Somatostatin (SST)
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