An international research group led by MedUni Vienna and IMBA – Institute of Molecular Biotechnology, Vienna, has made significant progress in understanding the mechanisms that influence the sensation of pain after surgical procedures. Currently available treatment methods for postoperative pain are sometimes associated with significant side effects and are often only effective to a limited extent. The findings currently gained show a new possibility for local and targeted therapy. The study has now been published in the renowned journal “Science Immunology”.
In its research, the team led by study leaders Philipp Starkl, Shane Cronin and Josef Penninger built on previous findings on the role of the substance tetrahydrobiopterin (BH4) in neuropathic pain: the higher the concentration of BH4, the stronger the nerve pain. “Whether this correlation also applies to postoperative pain has not yet been investigated,” says Josef Penninger (Clinical Institute of Laboratory Medicine at MedUni Vienna, IMBA, Helmholtz Center for Infection Research, Braunschweig), describing the initial situation of the study.
In a series of experiments on mouse models with surgically induced skin injuries and using novel analytical methods, the researchers brought to light both the central role of BH4 in postoperative pain and the underlying mechanisms. As it turns out, the innate immune system plays a crucial role. The signaling cascade starts in special immune cells (mast cells), which are positioned near pain-sensitive nerve cells in the skin and act as a production site for BH4 after an operation. “In mice whose mast cells did not produce BH4, we observed drastically reduced pain sensitivity after surgery. Conversely, it was shown that increased BH4 production by mast cells was associated with greater pain,” reports Shane Cronin (Clinical Institute of Laboratory Medicine at MedUni Vienna, IMBA) with details. With the key role of mast cells in the sensation of pain, the research team has also found a possible solution to the mystery surrounding the function of these cells in the body: “Until now, we mainly knew about their influence on allergic reactions and wondered why we have this cell type for hundreds of millions of years “We have retained evolution despite its harmful and dangerous role in allergies,” says Philipp Starkl (University Clinic for Internal Medicine I at MedUni Vienna), underlining the significance of the findings.
Active ingredient with potential developed
Pain is important in warning the body of danger and ensuring efficient healing after injury. However, in many cases, post-operative pain becomes chronic and persists for at least three months after the procedure, even though the body has already healed. Current treatment methods are sometimes associated with significant side effects and are often only effective to a limited extent. In the search for alternatives, research into the molecular and cellular mechanisms involved in postoperative pain has long been the focus of medical science. A promising approach has now been found by blocking BH4 production in mast cells. The team led by Starkl, Penninger and Cronin has already developed a therapeutic approach in which an active substance can be applied directly to the skin in order to specifically and prophylactically reduce the BH4 concentration. “We see great potential here for a local and targeted therapy option to reduce both postoperative pain and the likelihood that the pain will become chronic,” emphasize the study authors in advance of further studies that are intended to deepen and confirm the results.
Publikation: Science Immunology
Mast cell-derived BH4 and serotonin are critical mediators of 1 postoperative pain.
Philipp Starkl, Gustav Jonsson, Tyler Artner, Bruna Lenfers Turnes, Laura-Marie Gail, Tiago Oliveira, Aakanksha Jain, Nadine Serhan, Karel Stejskal, Karin Lakovits, Anastasiya Hladik, Meilin An, Keith M. Channon, Hail Kim, Thomas Köcher, Wolfgang Weninger, Georg Stary, Sylvia Knapp, Victoria Klang, Nicolas Gaudenzio, Clifford J. Woolf, Shweta Tikoo, Rohit Jain, Josef M. Penninger, Shane J.F. Cronin.
DOI: 10.1126/sciimmunol.adh0545