Neurobiologist discovers powerful pain control center in brain

A research team at Durham, North Carolina-Duke University has discovered that small areas of the mouse’s brain can significantly control the sensation of animal pain.

Somewhat unexpectedly, the center of this brain is off, not pain. It is also in an area of ​​distress and in an area where few would have been looking for an amygdala. The amygdala is considered the home of negative emotions and reactions, such as fighting, flight reactions and general anxiety.

“People believe there is a central place to relieve pain, which is why placebo works,” said Fan Wang, Morris N. Broad, a prominent professor of neurobiology at the School of Medicine. .. “The question is where is the center of the brain where pain can be eliminated.”

“Most of the research to date has focused on areas that are turned on by pain,” Wang said. “But there are so many areas that deal with pain that you need to turn them all off to stop the pain, while this one center alone can alleviate the pain.”

This study is a follow-up to a previous study in Wang’s lab that examined neurons that were activated rather than suppressed by general anesthesia. To 2019 research, They found that general anesthesia promotes slow-wave sleep by activating the supraoptic nucleus of the brain. But sleep and pain are different, and are key clues that led to a new discovery online in Nature Neuroscience on May 18th.

The researchers found that general anesthesia also activated inhibitory neurons in certain subsets of the central amygdala. These are called CeAga neurons (CeA represents the central amygdala and ga represents activation by general anesthesia). Although the central amygdala of mice is relatively larger than that of humans, Wang said there was no reason to think of another system for controlling pain.

Using technology pioneered by King’s lab to track the pathways of activated neurons in the mouse, the team discovered that CeAga is connected to many different areas of the brain. ..

By giving mice a mild pain stimulus, researchers were able to map the areas of the brain that were activated by all pain. They found that at least 16 brain centers known to process the sensory or emotional aspects of pain received suppressive input from CeAga.

“Pain is a complex brain reaction,” Wang said. “It includes sensory discrimination, emotions, and autonomic (involuntary nervous system) responses. In many areas, treating pain by dampening all these brain processes is something that can be achieved. It’s very difficult, but it becomes more robust when we activate the key nodes that naturally send inhibitory signals to these pain processing areas. ”

Using a technique called optogenetics that uses light to activate a small number of cells in the brain, the researchers show that self-regulation when mice feel uncomfortable by activating CeAga neurons. I have discovered that I can turn off the action. The act of licking the foot or wiping the face was “completely abolished” at the moment of turning on the light and activating the pain relieving center.

“It’s so dramatic,” said the king. “They immediately stop licking or rubbing.”

When scientists diminished the activity of these CeAga neurons, the mice responded as if the temporary seizures were re-intensified and painful. They also found that low-dose ketamine, a sensation-tolerant but pain-blocking anesthetic, activates CeAga centers and does not function without it.

Wang said the researchers are now looking for future painkillers that could activate only these cells to suppress pain.

“The other thing we’re trying to do is to sequence hell (transcriptome) from these cells,” she said. Among these specialized cells, researchers want to find a rare or unique cell surface receptor gene that enables highly specific drugs to activate these neurons and relieve pain. I think.

This work is based on the National Institutes of Health (DP1MH103908, R01 DE029342, R01 NS109947, R01 DE027454), Holland-Trice Scholar Award, W.M. Postdoctoral fellow at the Keck Foundation and the National Science Foundation.

Quote: “General anesthetic activates a powerful central nervous system inhibitory circuit of the amygdala” Thuy Hua, Bin Chen, Dongye Lu, Katsuyasu Sakurai, Shengli Zhao, Bao-Xia Han, Jiwoo Kim, Luping Yin, Yong Chen, Jinghao Lu, fan king. Nature Neuroscience, May 18, 2020. DOI: 10.1038 / s41593-020-0632-8