Excitation-transcription coupling alters activity of nociceptive neurons

• Applicants: Professor Dr. Pascal Falter-Braun; Professor Dr. Tim Hucho
• Subject Area: Anaesthesiology ; Anatomy and Physiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516750869

Persistent activity of peripheral nociceptive neurons drives central chronification of pain. But what drives peripheral persistent activity is not well understood. In the central nervous system (CNS), neuronal activity translates into persistently increased activity by so-called excitation-transcription (E-T) coupling. Based on our preliminary data, we aim to address the hypothesis that E-T coupling also regulates the activity of peripheral nociceptors and thus the process of pain chronification. We aim 1) to elucidate signaling pathways initiating E-T coupling in nociceptive neurons, 2) to identify neuronal functions regulated by E-T coupling, and 3) to identify their contribution to chronic pain. To address these aims, we will combine transcriptomic, pharmacological, and optogenetic approaches to understand how specific activity-patterns affect E-T coupling in subgroups of sensory neurons. The effect of E-T-induced changes for electrical activity as well as sensitization-signaling will be determined by MEA electrophysiology and high content screening microscopy in primary rodent nociceptors and human stem cell derived nociceptors. The role of the elucidated mechanisms in vivo and in pain chronification will be validated in animal pain models. It is plausible to assume that understanding of molecular mechanisms of pain chronification will enable fundamentally new preventative and therapeutic approaches.

• DFG Programme: Research Grants
• Major Instrumentation: Multi-Electrode-Array Electrophysiological recorder
• Instrumentation Group: 3440 Elektrophysiologische Meßsysteme (außer 300-309 und 340-343)
• Co-Investigator: Dr. Jörg Isensee