Project Details
Projekt
A protein fingerprint of postoperative pain in the incision model of mouse and human - A translational study
Subject Area
Experimental Models for the Understanding of Nervous System Diseases
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2018 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 397635414
Each year about 35-40 million people undergo surgery in Europe. Surgeries are often accompanied by postoperative pain which should be alleviated as soon as possible in order to promote the healing process and prevent complications. In addition to acute complications untreated acute postoperative pain develops into chronic pain in up to 50% of cases. Although established guidelines and evidence-based recommendations exist, postoperative pain remains predominantly undertreated. This is largely due to the fact that the underlying neuropathological mechanisms of postoperative pain are not well understood. A major but yet unmet goal in pain research is a translational approach in order to efficiently identify clinical relevant neuropathological changes and tranlate these findings to humans and to the clinical practice. Current pain research is increasingly resorted to methods in the fields of genomics and proteomics to identify global changes on different levels (proteins, genes) in peripheral, spinal and supraspinal areas of the nociceptive system. These data are expected to aid the identification of novel targets for therapeutics. Emerging technologies in the field of proteomics have the potential to provide unprecedented insights into proteome changes across different pain models in a standardized and reproducible fashion. Hence, the generation of a protein fingerprint specific for postoperative pain becomes a feasible endeavor. The focus of this study is to combine (almost identical) experimental pain models in human and mouse (translational approach) with emerging proteomics technologies in order to comprehensively detect and compare protein signatures of postoperative pain.Primary goals of this study:(1) Comprehensive protein profiling in DRG of mice after incision.(2) Bioinformatic comparison of the specific incision-modulated proteome of DRG from mice with previous data from an inflammatory and neuropathic animal model - What are the differences and similarities between the different pain entities?(3) Identification of the blood protein signature upon incision in humans and mice. Which similarities between proteomic changes can be found in the blood of mice and humans after incision? Are there significant differences between the two species? (4) Initial validation of mouse DRG candidate proteins in situ and in vitro.Outlook for future subsequent studies:(1) Assessment of the relevance of identified candidate proteins for the generation and maintenance of postoperative pain by means of mouse behavior studies (2) Use of pharmacological and optogenetic magnetic resonance imaging (MRI) experiments (phMRI; opMRT), and electrophysiological studies to characterize the function of identified candidate proteins in spinal and supraspinal structures.(3) Clinical studies on post-surgical patients to verify the clinical importance of candidate proteins in the context of prediction and treatment studies (complete translation to the patient).
DFG Programme
Research Grants
