Role of Gaq/11 signaling in activity-dependent peripheral sensitization

• Applicant: Dr. Anke Tappe-Theodor
• Subject Area: Pharmacology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215962548

The G-protein GPCR signaling is important in nociceptive modulation as well as in pain generation. A variety of key nociceptive modulators are known to activate GPCRs expressed on sensory nerves. Because these neuromodulators can activate the Gq/11, Gs, Gi/o as well as the G12/13 branches of G-protein signaling, the relative contribution and functional significance of the individual signaling pathways in modulation of nociceptor function in vivo is not clear. Using nociceptor-specific Gáq/11-deficient mice, we found recently that Gáq/11 signaling tonically modulates baseline nociceptor function, contributes to acute and chronic inflammatory sensitization and modulates voltage gated-sodium channels. In this project we plan to identify the mechanisms of Gáq/11-mediated modulation of voltage gated-sodium channels. Furthermore, we plan to perform profiling experiments to elucidate the role of Gáq/11 in gene regulation. Using patch-clamp electrophysiological recordings, we aim at investigating the influence of Gáq/11 signaling on nociceptor properties. We will unravel the individual role of Gáq and Gá11 in signal transduction in nociceptors and finally investigate the role of Gáq/11 in clinically relevant models of chronic pain. This project will deliver detailed insights into the functional contribution of Gáq/11 signaling in nociceptors towards the development of peripheral sensitization as well as the induction of central sensitization, which represents critically important aspects of the pathophysiology of chronic pain.

• DFG Programme: Research Grants