Stress and the Brain's Natural Painkillers: A New Way to Track Enkephalins

Enkephalins are like the brain's own painkillers. They help with pain relief, reward, and dealing with stress. But tracking them in real-time has been tough because they appear and disappear quickly and are present in tiny amounts. Scientists have come up with a clever way to study these enkephalins. They combined a few techniques: optogenetics, which uses light to control brain cells, microdialysis, which samples brain chemicals, and a super-sensitive mass spectrometry assay. This setup lets them measure enkephalin release in mice as they move around freely. The big breakthrough here is the improved detection method. It allows researchers to see changes in enkephalins right after a stressful event. They focused on two types of enkephalins, Met- and Leu-enkephalin, in a specific part of the brain called the nucleus accumbens shell (NAcSh). Using this new method, they confirmed that stress activates enkephalin-producing neurons in the NAcSh. This activation leads to the release of both Met- and Leu-enkephalin. What's cool is that they could see how these enkephalins are released over time and how they relate to each other. This was hard to do before because older methods looked at mRNA levels instead of the actual enkephalins. The new approach also improves the accuracy of detecting Met-enkephalin by using a trick called methionine oxidation. This gives scientists a better understanding of how these enkephalins behave after stress.