Scientists from the Moscow Institute of Bioorganic Chemistry named after Academicians M.M. Shemyakina and Yu.A. Ovchinnikov of the Russian Academy of Sciences (IBCh RAS) discovered a natural anti-analgesic in the human nervous system, which turned out to be the regulatory molecule nocystatin. According to experts, this will create a new generation of pain medications. The study was published in the journal Biomolecules and supported by the Russian Science Foundation.
The production of analgesics around the world is constantly expanding and requires the development of new approaches to creating highly effective drugs with minimal side effects, the researchers note. The attention of Russian biochemists searching for effective painkillers was drawn to the nocystatin compound, one of the opioid neuropeptides secreted by the nervous system (a type of protein molecule). For a long time, the role of this regulatory molecule remained a mystery to scientists. Her presence influenced the processes of pain relief, but how - it was not clear. Domestic specialists managed to prove that nocystatin interacts with ion channels located on the shells of the body’s cells, which are sensitive to the pain-causing process - acidification of the intercellular substance.
“We still have much to learn about the regulation of the onset and termination of pain at the molecular level. Now that such an unusual function of nocystatin has been discovered, interest in studying molecules of the same class may increase. We hope to come to a new understanding of the mechanism for enhancing and alleviating pain and in the future to creating more effective analgesics that are not addictive, ”said Sergey Kozlov, head of the Laboratory of Neuroreceptors and Neuroregulators at the Institute of Chemistry, Russian Academy of Sciences.
The action of analgesics is aimed at drowning out signals from the source of inflammation or trauma to the central nervous system. Information transmitted through the nerves is an electric current pulse that travels along the cell walls. On the surface of each cell are ion channels (ASIC channels) that are able to recognize signal molecules and trigger an electrical signal in new cells, that is, transmit information about pain along a chain. These channels resemble gates, but to open them, you need to pick up a special key, the researchers note.
Scientists added nocystatin molecules to the intercellular substance in vitro. This unexpectedly led to a chain reaction - activation of ion channels, which began to behave in the same way as during painful acidification of the space between the cells. Such an effect was discovered for the first time, since previously all known molecules capable of interacting with ASIC could only change the strength or time of opening of channels.
“When the intercellular space becomes acidic, it hurts us. This is a signal that unwanted processes are occurring in the body. For example, acidification of the environment causes diseases of the gastrointestinal tract, benign and malignant tumors, and other inflammations of organs. Nocistatin acts instead of acid, but it may not cause pain. Now we need to roll up our sleeves and continue studying it on animal models, ”said Sergey Kozlov in an interview with RT.
According to the scientist, the discovery of the mechanism of action of nocystatin on the ion channels will allow not only the development of new drugs for pain, but also reduce the harm from existing drugs, including narcotic drugs - opioids. Also, the work will help to cope with the tolerance of the body - getting used to such substances, the biochemist believes.