Prof. Dr. Stefan Lechner
Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
Prof. Dr. Martin Schmelz
Department of Experimental Pain Research, Medical Faculty Mannheim, Heidelberg University
Structure-function properties and markers of silent nociceptors in mice and humans
This project will focus on mechano-insensitive nociceptors, which become sensitized during inflammation. We have identified a molecular marker for these so-called ‘silent’ nociceptors, which for the first time enables us to thoroughly characterize the functional properties of these afferents and the signalling cascades that mediate sensitization during inflammation as well as their role in the induction and maintenance of mechanical hyperalgesia under pathological conditions. To this end we will utilize intersectional genetics (cell ablation, optogenetics and DREADD technology) in combination with electrophysiological techniques (patch-clamp, in-vitro skin-nerve recordings and spinal cord slice recordings) and behavioural assays.
An important goal of this project is to test the clinical relevance of results obtained from experiments in mice in human studies.
Hence, in corresponding human experiments characteristics of silent nociceptors and their sensitization by inflammatory mediators will be studied using microneurography and psychophysics to allow for bidirectional translation. Based on functional differences of nociceptor classes, specific excitability tests are being developed that work on single cell level, but also in ex-vivo preparations of peripheral nerves and in human volunteers and pain patients. The long-term perspective of this project is the identification of specific targets on silent nociceptors that enable control of their excitability in order to provide new analgesic approaches in animal models and finally in pain patients.