Researchers from the Heidelberg Pain Consortium, Prof. Martin Schmelz ( project A01) and Dr Hans Jürgen Solinski ( Project  Z02-INF) have contributed to a landmark international study published in Cell, uncovering the molecular identity of human dermal “sleeping nociceptors.” This major scientific advance provides long-awaited insight into a key class of sensory neurons implicated in chronic pain and itch, and establishes an important foundation for the development of future targeted therapies. The publication highlights the strength of interdisciplinary collaboration within the Heidelberg Pain Consortium and its strong integration into international research networks. Read More (hyperlink and then the following text will appear)

Approximately 10-20% of the population suffer from chronic pain or itch, which are frequently associated with spontaneous activity of sleeping nociceptors. These neurons can become spontaneously active to cause persistent pain or itch even without an external stimulus. Strikingly, inflammation can awaken the mechano-sensitivity of these neurons, completely altering their physiological phenotype. Although the functional properties of these fibers have been known for many years, their molecular identity remained unclear, thereby lacking a critical prerequisite for the development of targeted therapeutic interventions.

Prof. Martin Schmelz and Dr. Hans Jürgen Solinski from the Department of Experimental Pain Research (Mannheim Center for Translational Neuroscience) joined an international research team, led by Prof. Angelika Lampert (RWTH Aachen) and Dr. Shreejoy Tripathy (University of Toronto), that has now closed this key knowledge gap. By combining high-resolution electrophysiological recordings with techniques that read the genetic activity of individual neurons (RNA-sequencing), the researchers identified a clearly defined neuronal population with sleeping nociceptor properties. Importantly, the team used pigs as a key translational model, as pigs possess sleeping nociceptors in their skin that closely resemble those found in humans.

The team’s analyses reveal that sleeping nociceptors are defined by a specific molecular signature, which includes, among other components, the oncostatin M receptor (OSMR) and the neuropeptide somatostatin (SST). Co-second author Dr. Solinski comments: “It was a great surprise to find this neuron-type had sleeping nociceptor properties, as it was previously implicated in the detection of various forms of chemical itch in mice and mice do not possess dermal sleeping nociceptors. Our work is therefore a good example of how interdisciplinary collaboration can overcome existing thematic boundaries and methodological hurdles.” Amongst others, the voltage-gated sodium channel NaV1.9 (SCN11A), highly expressed in and functionally important for sleeping nociceptors, was identified as an interesting new drug target that might be exploited to quiet these neurons in the context of chronic itch or pain.

Finally, the team translated their findings back to humans by performing self-experiments on several senior study authors. These experiments clearly showed that oncostatin M, which activates OSMR, specifically modulates sleeping nociceptors in the human skin, confirming the molecular predictions obtained in pigs directly in humans. Collectively, the team established a new conceptual framework for understanding the emergence of neuropathic pain and itch at the molecular level: This will open concrete perspectives for the development of new, targeted therapies in the future.

Silent nociceptors have been the central research theme of Prof. Schmelz’ scientific career. He thus appreciates the particular visibility cast on this topic and on CRC 1158 by this prestigious publication. Reflective of the intense collaboration in our CRC, he also highlights: “This work was only possible by a large research team, demonstrating the power of interdisciplinary and international cooperation. The success of the study relied on the close integration of specialized centers in Germany, Canada, London and the United States”.

*Publication

Körner J, Howard D, Solinski HJ et al. Molecular architecture of human dermal sleeping nociceptors.2026, Cell 189, 1–16

March 19, 2026 © 2025 The Authors. Published by Elsevier Inc

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