Recent research data could help develop the next generation of pain relievers.
A Duke University research team has discovered a small region of the brain in mice that can deeply control pain. An article about this was published in Nature Neuroscience.
The most unusual thing about this find is its location, given that this brain center turns off pain, rather than turning it on. It is located in the amygdala, a region often considered the home of negative emotions and reactions such as fight or flight and general anxiety.
"People believe there is a central place for pain relief, which is why placebos work," explained senior author, neuroscience professor Fan Wang. "The question is where exactly in the brain is the center that can shut off pain."
Most of the previous studies looking for areas of the brain responsible for pain regulation have found separate centers of regulation. There are many of them, and they lie in different parts of the brain: in order to "turn off" pain with their help, you need to turn off more than one. This same center is similar to a "central switch" and allows you to turn off the pain only by changing the activity in it alone.
The new work follows on from earlier research in Wang's lab to study neurons that are activated rather than suppressed when using general anesthesia. In a 2019 study, researchers found that general anesthesia promotes slow-wave sleep by activating the brain's supraoptic nucleus. It was this that prompted them to hypothesize, which was confirmed in the new work.
The researchers found that general anesthesia also activates a specific subset of inhibitory neurons in the central amygdala, which they called CeAga neurons (CeA stands for central amygdala; ga indicates activation by general anesthesia). Mice have a relatively large central amygdala compared to humans, but according to Professor Wang, there is no reason to believe we have a different system for pain control.
Using technology that Wang's lab pioneered to track the pathways of activated neurons in mice, the team found that CeAga was associated with many different areas of the brain, "which was unexpected."
By giving the mice a mild pain stimulus, the researchers could map out all of the pain-activated areas of the brain. They found that at least 16 brain centers known to process sensory or emotional aspects of pain received inhibitory information from CeAga.
“Pain is a complex brain response,” Wang explains. It includes sensory discrimination (the ability to distinguish two or more with the help of the senses. - Ed.), Emotions and autonomic responses (involuntary response of the nervous system). Treating pain by weakening all of these brain processes in many areas is difficult to achieve. But activating a key node that naturally sends inhibitory signals to regions to process pain would be a more successful option.”
Using optogenetic technology that uses light to activate a small population of cells in the brain, the researchers found that they could turn off the neurotic responses that mice normally experience when they feel uncomfortable by activating CeAga. This behavior, such as licking paws or rubbing the muzzle, was completely canceled at the moment when the light was turned on to activate the pain center.
When the scientists weakened the activity of CeAga neurons, the mice reacted as if the weak stimulus became more intense, more painful, although in fact its intensity did not change. Researchers also found that low doses of ketamine - an anesthetic that allows you to feel sensation but blocks pain - activate the CeAga center and won't work without it.
The team's further goals are to find drugs that will only activate these cells to suppress pain. These drugs have the potential to be the next generation of pain relievers.
In addition, the authors consider another avenue of research for the development of new pain relievers. This requires finding a gene for a rare or unique cell surface receptor among these specialized cells that would allow a very specific drug to activate such neurons and relieve pain.