US, WASHINGTON (ORDO NEWS) — A research group from Duke University has discovered a small area of the mouse brain that can deeply control the feeling of pain. An article about this is published in Nature Neuroscience.
The most unusual thing about this find is its location, given that this brain center turns off the pain, not turns it on. It is located in the amygdala, a department that is often considered the “home” of negative emotions and reactions, such as hit or run and general anxiety.
“People believe that there is a central place for pain relief, so a placebo works,” explained Phan Wang, senior author of the work, professor of neuroscience. “The question is where exactly in the brain is the center that can turn off the pain.”
Most of the previous studies aimed at finding areas of the brain responsible for regulating pain have found separate centers of regulation. There are many of them, and they lie in different parts of the brain: to “turn off” the pain with their help, you need to turn off more than one. The same center is similar to the “central switch” and allows you to turn off the pain only by changing the activity in it alone.
The new work was a continuation of earlier studies in Wang’s laboratory for the study of neurons that are activated, rather than suppressed, using general anesthesia. In a study conducted in 2019, scientists found that general anesthesia promotes slow-wave sleep by activating the supraoptic core of the brain. That is what prompted them the hypothesis, confirmed in a 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 that we have a different system for controlling pain.
Using technology that Wang’s laboratory first applied to track the pathways of activated neurons in mice, the team found that CeAga was connected to many different areas of the brain, “which was unexpected.”
By giving mice a mild pain stimulus, researchers could display all pain-activated areas of the brain. They found that at least 16 brain centers, which are known to handle the sensory or emotional aspects of pain, received inhibitory information from CeAga.
“Pain is a complex brain reaction,” Wang explains. It includes sensory discrimination (the ability to distinguish between two or more using the senses. – Ed.), Emotions and autonomic reactions (involuntary response of the nervous system). The treatment of pain by attenuating all these brain processes in many areas is difficult to achieve. But activating a key node that naturally sends regions inhibitory signals for pain management would be a more successful option.”
Using optogenetic technology that uses light to activate a small population of cells in the brain, researchers found that they can turn off the neurotic reactions that usually occur in a mouse when CeAga activates it when it feels uncomfortable. This behavior, such as licking the paws or rubbing the muzzle, turned out to be completely canceled at the moment when the light was turned on to activate the analgesic center.
When scientists weakened the activity of CeAga neurons, the mice reacted as if a weak stimulus had become more intense, more painful, although in fact its intensity did not change. Researchers also found that low doses of ketamine, an anesthetic that leaves you unable to feel, but blocks pain, activate the CeAga center and will not work without it.
Further goals of the team – the search for drugs that will activate only these cells to suppress pain. Potentially, these drugs can become a new generation of painkillers.
In addition, the authors are considering another direction of search for the creation of new painkillers. To do this, you need to find a rare or unique cell surface receptor gene among these specialized cells, which would allow a very specific drug to activate such neurons and relieve pain.
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