Project Details
Projekt
Neuropathic pain induced by anti Caspr2 autoantibodies: pathogenesis and resolution
Subject Area
Molecular and Cellular Neurology and Neuropathology
Anaesthesiology
Anaesthesiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426503586
Autoantibodies against Caspr2, a protein of the voltage-gated potassium channel complex, are supposed to induce neuropathic pain by binding to DRG neurons leading to hyperexcitability of nociceptive neurons. However, only about one third of the patients with anti-Caspr2 autoantibodies experience pain and even pain resolution varies. By performing functional readouts, we could demonstrate hyperexcitability of neurons exposed to anti-Caspr2 autoantibodies. Correlation of these data with the IgG subclass and pain phenotyping provided evidence, that additional mechanisms induce neuronal hyperexcitability and account for different pain phenotypes and resolution. Immune complexes that bind to FcγR1 on nociceptive neurons may contribute to hyperexcitability and thereby participate in pain resolution. In the planned project, pain phenotyping (including resolution), hyperexcitability induced by pure IgG and immune complexes and effects on the transcriptome are investigated and correlated to unravel the pathophysiology of anti-Caspr2-mediated neuropathic pain and its resolution. To transfer our insights to a broader range of autoantibody-mediated pain conditions, some experiments will be expanded to sera of patients with anti-paranodal autoantibodies and neuropathic pain, pursuing the overall aim to disclose new therapeutic targets for autoantibody-mediated neuropathic pain that promote pain resolution.
DFG Programme
Clinical Research Units
