Project Details
Projekt
Presynaptic and peripheral plasticity of nociceptors in pain resolution
Subject Area
Molecular and Cellular Neurology and Neuropathology
Anaesthesiology
Molecular Biology and Physiology of Neurons and Glial Cells
Anaesthesiology
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426503586
The proposed project will investigate presynaptic and peripheral plasticity of nociceptors in pain resolution. The translational studies will be conducted in Drosophila, to elucidate basic molecular mechanisms, in rodents with transient neuropathy, and in CRPS patients. A genetic screen in FP1 has identified multiple proteins required for resolution from chemotherapy-induced hyperalgesia. Moreover, the results highlight that both nerve terminals of nociceptors as well as the presynaptic active zone undergo plastic changes at the molecular level during the resolution process. The planned work program aims to obtain a better mechanistic understanding of the underlying mechanisms through interdisciplinary structure-function analyses. The first two work packages will carry out experiments in Drosophila to study the function of proteins necessary for resolution (WP1) and to investigate presynaptic plasticity of nociceptors during resolution of bortezomib-induced pe-ripheral neuropathy (BIPN; WP2). Matching the experiments in Drosophila, the second two work packages will study the peripheral and central endings of mammalian nociceptors at the subcellular level. We aim to examine across diseases whether altered expression of ion channels, identified in the Drosophila BIPN screen, shapes pain and its resolution process in the peripheral tissue (WP3). In the spinal cord, we will focus on nociceptor synapses onto projection neurons in superficial lam-inae of the dorsal horn (WP4). We hypothesize that plastic molecular reorganisations of the presynaptic active zone shape pain and pain resolution in BIPN and chronic constriction injury (CCI). We anticipate that this project will shed light on molecular mechanisms underlying nociceptor plastici-ty and uncover new therapeutic targets in the peripheral pain pathway.
DFG Programme
Clinical Research Units
