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KFO 5001:  Peripheral mechanisms of pain and their resolution

Subject Area Medicine
Term since 2020
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 426503586
 
Resolution of and recovery from neuropathic pain are active processes which depend on mechanisms such as resolution of inflammation and restoration of neuronal pathways. The fact that pain from a nerve lesion may subside without complete anatomical and physiological recovery indicates that this is a tightly regulated process. If this self-healing process is disturbed, chronic pain may ensue, e.g. chronic postoperative pain. Answering the question, why pain resolves in some patients after a nerve lesion despite persistent neurological deficits, and why chronic postoperative pain subsides in some and remains in others, will bring us closer to targeted efficient treatments. Here, we aim to investigate recovery patterns and mechanisms of pain resolution in the peripheral somatosensory system. We will utilize a combined translational approach involving clinical, preclinical, and basic sciences as well as pilot studies on CNS control over the peripheral processes. The Clinical Research Unit “Peripheral mechanisms of pain and their resolution” (ResolvePAIN) will use a top-down approach centered around patients and a bottom-up approach including cellular models, model organisms involving flies and rodents in a combined multi-level effort. The clinical model diseases all share the hallmark that recovery occurs in some patients but not in all. We will use a cross-sectional and longitudinal design to clinically phenotype and follow up patients with neuropathic pain states after surgery/trauma, chemotherapy, autoimmunity and in a genetic disease. We will set up core units for innovative methods of human nerve and dorsal-root-ganglion imaging (MR Neurography), skin and blood biomaterial analysis, using a uniform database, to identify disease subgroups and clinical patterns of pain resolution. Three matched preclinical resolution models, traumatic nerve injury, autoantibody transfer- and chemotherapy-induced neuropathy, as well as resolution paradigms in neuronal/non-neuronal cellular systems and flies will be employed. We will characterize peripheral mechanistic pain patterns and networks and their resolution using a combination of targeted and unbiased approaches. Targets involve neuroinflammation, ion channel function, cell-cell contacts, neurotrophic and neuronal guidance factors, oxidized lipids, genetics and epigenetics as well as CNS control of the periphery as exemplified in the social dimension of pain. To reach this end sustainably, ResolvePAIN will foster clinical and scientific education of a new generation of Clinician Scientists in anesthesiology, neurology, neuroradiology, neurosurgery, surgery, and internal medicine in a pain class of the “Integrative Clinician Scientists College” Würzburg. Understanding recovery from neuropathic pain states will help to identify subgroups of patients at risk and in need of personalized intensified treatment and new molecular treatment targets to promote recovery in neuropathic pain states.
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