2024-08-23 18:00:18
An international research team led by MedUni Vienna and IMBA (Institute of Molecular Biotechnology Vienna) has made significant progress in understanding the mechanisms that influence the perception of pain after surgery. Currently available treatments for postoperative pain sometimes produce significant side effects and are often only effective to a limited extent. The knowledge gained so far shows new possibilities for local and targeted treatments. The research has now been published in the prestigious journal Science Immunology.
In this study, a team led by study leaders Philipp Starkl, Shane Cronin and Josef Penninger built on previous findings about the role of the substance tetrahydrobiopterin (BH4) in neuropathic pain: the higher the concentration of BH4, the more The pain becomes more intense. “Whether this correlation also applies to postoperative pain has not yet been investigated,” says Josef Penninger (Institute of Clinical Experimental Medicine, Medical University of Vienna, IMBA, Helmholtz Center for Infection Research, Braunschweig), describing the preliminary results of the study. Say the situation.
In conducting a series of experiments on a mouse model of surgery-induced skin injury and using novel analytical methods, the researchers revealed the central role of BH4 in postoperative pain and its underlying mechanisms. It turns out that the innate immune system plays a crucial role. The signaling cascade begins with specialized immune cells (mast cells) that are located near pain-sensitive nerve cells in the skin and serve as BH4 production sites after surgery. “In mice whose mast cells do not produce BH4, we observed a significant decrease in pain sensitivity after surgery. In contrast, studies have shown that increased BH4 production by mast cells is associated with greater pain,” said Shane Cronin (Clinical Experiment, Medical University of Vienna) Institute of Medicine, IMBA) detailed report. Given the key role of mast cells in pain perception, the team also found a possible answer to the mystery of how these cells function in the body: “So far, we have mainly understood their impact on allergic reactions and wondered why we have this The cell type evolved over hundreds of millions of years “despite its harmful and dangerous role in allergies, which we have preserved,” says Philipp Starkl (First University Clinic of Internal Medicine, Medical University of Vienna), underscoring the importance of this discovery .
Active ingredients with development potential
Pain is important in warning the body of danger and ensuring effective recovery after injury. However, in many cases, post-surgery pain can become chronic and last for at least three months, even after the body has healed. Current treatments sometimes produce significant side effects and are often only effective to a limited extent. In the search for alternatives, the study of the molecular and cellular mechanisms of postoperative pain has long been a focus of medical science. A promising approach has now been discovered that blocks BH4 production in mast cells. A team led by Starkl, Penninger and Cronin has developed a treatment that applies active substances directly to the skin to specifically and preventively reduce BH4 concentrations. “We see here great potential for local and targeted treatment options to reduce postoperative pain and the likelihood of pain becoming chronic,” the study authors stressed, ahead of further studies aimed at deepening and confirming the results.
Publication: Scientific Immunology
Mast cell-derived BH4 and serotonin are critical mediators of postoperative pain.
Philipp Starkl, Gustav Jonsson, Tyler Artner, Bruna Lenfers Turnes, Laura-Marie Gail, Tiago Oliveira, Aakanksha Jain, Nadine Serhan, Karel Steannonkal, Karin Lakovits, Anastasiya Hladik, Meilin An, Keith M. Channon, Hail Kim, Thomas Köcher, Kim, Kim, Thomas Köcher, Wolfgang Weninger, Georg Starry, Sylvia Knapp, Victoria Crown, Nicholas Gaudenzio, Clifford J. Woolf, Shweta Tikoo, Rohit Jain, Joseph M. Penninger, Shane J.F. Cronin.
DOI: 10.1126/sciimmunol.adh0545
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