Presynaptic and Peripheral Plasticity of Nociceptors in Pain Resolution
By studying molecular and structural changes of nociceptor terminals from Drosophila to rodents and humans, the project seeks to uncover mechanisms that contribute to pain resolution and identify potential therapeutic targets.
Background
The resolution of chronic pain involves complex plasticity processes in nociceptors. Data from the first funding period have demonstrated that molecular reorganizations occur at peripheral terminals and presynaptic endings of nociceptors, influencing pain persistence and its resolution. Genetic screening in Drosophila identified key proteins involved in resolution from chemotherapy-induced neuropathy. Translational studies in rodent models and in patients with Complex Regional Pain Syndrome (CRPS) and bortezomib-induced peripheral neuropathy (BIPN) indicate that similar mechanisms may operate in mammals, suggesting an evolutionary conservation of these pathways.
Research Objective
This project will explore molecular and structural plasticity of nociceptor terminals in Drosophila, rodents, and humans, focusing on peripheral and presynaptic changes that modulate resolution using high resolution imaging and electrophysiological and optogenetic functional characterization using genetic manupulations. Special attention will be given to ion channels and synaptic proteins identified in prior screens in Drosophila.
Significance
By elucidating the presynaptic and peripheral mechanisms involved in nociceptor plasticity, this project will contribute to a better mechanistic understanding of pain resolution processes. The findings may lead to the identification of novel therapeutic targets to promote recovery from chronic neuropathic pain.
Research Team P6
Principal investigators
Univ.-Prof. Dr. Robert Kittel
Department of Animal Physiology, Institute of Biology
Leipzig University
Univ.-Prof. Dr. Heike Rittner, MD
Scientific Coordinator KFO5001
Chair Centre for Interdisciplinary Pain Medicine
Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine
University Hospital Würzburg
Members of the team
Dr. Mareike Selcho, PhD, Researcher
Mariam Atalla, PhD Student
Dr. Divya Sachidanandan, PhD, Researcher
