ZIB Researchers Help to Understand Cellular Processes Related to Pain Relief Drugs – Results Published in Nature
Pain relief therapy is one of most important sectors of the health care system with 12-15 million patients with chronic pain, including 5 million with severe pain in Germany alone. Opioid receptors play a major role in the treatment of severe pain: world-wide more than 100 million patients use drugs based on opioid ligands (like Tramadol or Fentanyl), despite their severe side effects. These numbers are growing. Thus, a better understanding of the biomedical function of the opioid receptor system is of high relevance to society and to millions of patients hoping for relief.
In a research article published by Nature Chemical Biology, an interdisciplinary team of experimentalists and mathematicians from Berlin University Hospital Charité, the Max-Delbrück Center for Molecular Medicine, Freie Universität Berlin and ZIB show that single-molecule microscopy combined with super-resolution techniques on intact cells and advanced mathematical modelling allows to understand how dimer formation of mu-opioid receptors is influenced by specific agonists. The results suggest a new level of GPCR regulation that links dimer formation to specific agonists and their downstream signals, thus opening a path to new pain relief drugs.
J.Moeller, A. Isbilir, T. Sungkaworn, B. Osberg, C. Karathanasis, V. Sunkara, E. O. Grushevskyi, A. Bock, P. Annibale, M. Heilemann, C. Schuette, and M. J. Lohse. Single molecule mu-opioid receptor membrane-dynamics reveal agonist-specific dimer formation with super-resolved precision. Nature-Chemical Biology, 2020. DOI: 10.1038/S41589-020-0566-1
[Researchers in italics receive MATH+ funding]