Mechanisms of heat- and acidosis-induced pain

A fundamental aspect of medical practice is the alleviation of pain. Many different drugs are available for this purpose, but they are often insufficiently effective, or their use leads to side effects. For this reason, novel pain-relieving drugs are needed. For these to be developed, a fundamental understanding of pain generation is necessary. However, much is still unclear. Therefore, the goal of this project is to better understand mechanisms of pain generation. The signals interpreted by the brain as pain usually originate at the ends of nerve cells called sensory neurons. These conduct signals from different parts of the body, e.g. the skin, towards the brain. At t he peripheral ends of these nerve cells, e.g. on the surface of the skin, there are proteins in the form of a watergate. These change their spatial arrangement due to physical (e.g. heat) or chemical stimuli (e.g. acid) and thus open up. This allows electrically charged particles, e.g. the positively charged sodium ion, to flow into the nerve cell. As soon as enough electrically charged particles have flowed into the nerve cell, the electrical signal is generated, which is now conducted towards the brain. It is obvious that one could eliminate the generation of pain by preventing the opening of these watergate-like proteins. However, there are many different ones, and it is not known exactly which proteins contribute to which type of pain. Therefore, this project is investigating which protein molecules contribute to pain from heat or from acid. What makes understanding how pain is triggered even more challenging is that in inflammation, the mechanisms are likely to be altered. Most are familiar with the phenomenon when lukewarm water triggers pain after a sunburn or when a gentle touch in the area of nail bed inflammation is highly painful. For this reason, the role of these proteins is also being investigated in inflamed tissue. Thus, this project expands our understanding of pain generation and lays the foundation for the development of new pain-relieving drugs.