Scientists identify a central pain-suppression circuit in mice

Written by Sharon Salt, Senior Editor

A team from Duke University (NC, USA) has identified a small area of the brain in mice that can ‘profoundly’ control the animals’ sense of pain.

The results, which have been published in Nature Neuroscience, reveal that this brain center is located in the amygdala and turns pain off, rather than on.

“Most of the previous studies have focused on which regions are turned ON by pain. But there are so many regions processing pain, you’d have to turn them all off to stop pain. Whereas this one center can turn off the pain by itself,” commented senior author of the study, Fan Wang (Duke University).

The current study is a follow-up to earlier research that was conducted in Wang’s lab, which examined neurons that were activated, as opposed to suppressed, by general anesthetics. In 2019 they found that general anesthesia was able to promote slow-wave sleep by activating the supraoptic nucleus of the brain. However, as sleep and pain are separate, this provided the team with a clue for their current study.

Within their study, the investigators found that general anesthesia was able to activate a subset of neurons located in the central amygdala, which they have termed ‘CeAga’ neurons. To their surprise, when the team tracked the paths of activated neurons in mice, they found that CeAga was connected to many different areas of the brain.

When the mice received a pain stimulus, the researchers were able to map all of the brain regions that were activated. They noted that at least 16 brain centers known to process the sensory or emotional aspects of pain were receiving inhibitory input from the CeAga.

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“Pain is a complicated brain process. 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,” explained Wang.

By using optogenetics, the team found that they could turn off certain behaviors that mice exhibit when feeling uncomfortable (e.g., paw licking or face wiping). Once the light was switched on to activate the anti-pain center, these self-caring behaviors were ‘completely abolished’.

When the activity of these CeAga neurons were dampened, the mice responded as if a temporary insult had become intense or painful again. The scientists also found that low-dose ketamine was able to activate the CeAga center and wouldn’t work without it.

In the future, the researchers hope to find potential pain killers that can activate these cells to suppress pain. Additionally, they want to sequence these cells to find a unique cell surface receptor that would enable for a very specific drug to activate these neurons and relieve pain.

Sources: Hua T, Chen B, Lu D et al. General anesthetics activate a potent central pain-suppression circuit in the amygdala. Nat. Neurosci. doi:10.1038/s41593-020-0632-8 (2020) (Epub ahead of print); https://today.duke.edu/2020/05/neurobiologist-finds-potent-pain-suppression-center-brain