Neurobiologists Discover an “On/Off” Switch for Pain

The central amygdala houses a pain-suppression circuit that can “turn off” pain.

Posted May 24, 2020

SciePro/Shutterstock
Source: SciePro/Shutterstock

Researchers at Duke University recently identified specific neurons in the central amygdala that appear to "turn off" pain during general anesthesia, even if there is no loss of consciousness. This research in mice zeroes in on a distinct population of GABAergic neurons that activate a potent pain-suppression circuit. These findings (Hua et al., 2020) were published on May 18 in the journal Nature Neuroscience

The first public demonstration of general anesthesia (GA) was in 1846 at Harvard's Massachusetts General Hospital in Boston. Although general anesthetics have been used for centuries to silence patients' perceptions of pain during surgery, the exact mechanism by which GA turns off pain has remained one of medicine's great mysteries until now. 

"Most of the previous studies have focused on which regions are turned ON by pain," [sic] senior author Fan Wang said in a news release. "But there are so many regions processing pain, you'd have to turn them all off to stop pain. Whereas this one center [in the amygdala] can turn off the pain by itself." Wang is a neurobiology professor at Duke's School of Medicine and founding director of the Wang Lab.

Wang's lab at Duke has pioneered state-of-the-art optogenetic techniques that can turn specific neurons on and off during lab experiments in mice. For this study, they started by giving mice a mild pain stimulus and mapped a multitude of different pain-activated brain regions.

Surprisingly, the researchers found that the inhibitory GABAergic neurons in the central amygdala were linked to at least 16 different brain centers known to process different aspects of pain. Although this research was in mice, Wang speculates that there is "no reason to think we [humans] have a different system for controlling pain."

These GABAergic neurons in the central amygdala acted like a toggle switch that could suppress or exacerbate pain. When these neurons were turned "on" using optogenetics, pain was significantly dampened. Conversely, when these neurons were turned "off" using optogenetics, sensations of pain were amplified. Based on their findings, the authors conclude: "Our study points to [these GABAergic neurons] as a potential powerful therapeutic target for alleviating chronic pain."

"Pain is a complicated brain response," Wang explains. "It involves sensory discrimination, emotion, and autonomic (involuntary nervous system) responses. Treating pain by dampening all of these brain processes in many areas is very difficult to achieve. But activating a key node that naturally sends inhibitory signals to these pain-processing regions would be more robust."

The next phase of Wang's research is focused on identifying specific ways to target these cells with pharmaceuticals that could eventually be used by humans as pain killers.

As Wang states bluntly in the news release: "The other thing we're trying to do is to (transcriptome) sequence the hell out of these cells." Wang and her team are thoroughly transcriptome sequencing these GABAergic neurons in the central amygdala with the hope of finding a unique receptor on the cell's surface that would allow a novel drug to activate this pain-suppression circuit.

Sometime in the near future, the latest discovery of a new way to turn off pain by targeting the GABAergic neurons in the central amygdala could turn out to be a game-changer for millions of people living with chronic pain.

References

Thuy Hua, Bin Chen, Dongye Lu, Katsuyasu Sakurai, Shengli Zhao, Bao-Xia Han, Jiwoo Kim, Luping Yin, Yong Chen, Jinghao Lu, Fan Wang. "General Anesthetics Activate a Potent Central Pain-Suppression Circuit in The Amygdala." Nature Neuroscience (First published: May 18, 2020) DOI: 10.1038/s41593-020-0632-8