Medical

Single off-switch found to dampen multiple pain centers in the brain

Single off-switch found to dam...
In experiments using mouse models, scientists have found neuron cells in the central amygdala of are linked to more than a dozen pain response regions in the brain
In experiments using mouse models, scientists have found neuron cells in the central amygdala of are linked to more than a dozen pain response regions in the brain
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CeAga neuron cells, colored red, magenta and yellow, in the central amygdala of a mouse brain
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CeAga neuron cells, colored red, magenta and yellow, in the central amygdala of a mouse brain
In experiments using mouse models, scientists have found neuron cells in the central amygdala of are linked to more than a dozen pain response regions in the brain
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In experiments using mouse models, scientists have found neuron cells in the central amygdala of are linked to more than a dozen pain response regions in the brain

What drives pain and how it might be prevented in humans are complex questions demanding complex answers, but scientists at Duke University have come across a rather simple one, comparatively speaking. The researchers have discovered that a small region of the brain can be leveraged to turn down activity in more than a dozen pain-promoting centers in mice, raising hopes of a highly efficient therapy that targets a single population of cells.

The research at Duke University builds on earlier work exploring the effects of general anesthesia on neurons, and which ones it activates rather than suppresses. This led to the discovery that general anesthesia can fire up a set of inhibitory neurons in the central amygdala, a brain region considered to be the control center for negative emotions.

The researchers dubbed these CeAga neurons, and using advanced imaging techniques pioneered by themselves, were able to trace their activity throughout the brains in mice. This led to the surprising discovery that these neurons in the central amygdala were connected to many different regions of the brain.

In further experiments, the team gave mice a mild pain stimulus and observed all the regions of the brain that were activated in response. In doing so, they found that at least 16 of them were being inhibited to some degree by the CeAga neurons. And this is where the discovery has so much potential in the eyes of the researchers, with the ability to possibly turn down a wide range of pain responses through a single mechanism.

“Pain is a complicated brain response,” says senior author Fan Wang. “It involves sensory discrimination, emotion, and 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 team explored the effects of targeting the CeAga neurons through what is known as optogenetics, where light is used to activate specific sets of cells. Activating the neurons had the effect of turning off typical behaviors exhibited by mice in discomfort, such as paw-licking and face-wiping, the moment the anti-pain center was exposed to the light.

“It’s so drastic,” Wang says. “They just instantaneously stop licking and rubbing.”

Conversely, the team found that when they dampened the activity of the CeAga neurons, the mice promptly began exhibiting signs of pain once again. All of this suggests the CeAga neurons could be a powerful target for treatments of chronic pain, and the researchers are now working to uncover drugs that target those cells specifically.

“People do believe there is a central place to relieve pain, that’s why placebos work,” says Wang. “The question is where in the brain is the center that can turn off pain. 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.”

The research was published in the journal Nature Neuroscience.

Source: Duke University

7 comments
Sean Reynolds
You know that is how leprosy works right? It shuts off your touch sensation which is tied to your pain sensation (just different intensity) and then people walk around and hurt themselves repeatedly till they die, because they can't feel. I guess I'm just saying... oh neat... be careful. :)
guzmanchinky
This would be incredible. Imagine a life without chronic pain for so many people who suffer, especially in old age.
IvanWashington
this can't come to market soon enough.
Ruth Fitzgerald
Awful to think of the suffering inflicted on animals in these experiments.
Karmudjun
I wonder if this research in any way ties in with the few painless individuals who were born without pain awareness or understanding. We have been trying to get to their lack of pain awareness for decades thinking duplication of their neural physiology (ie - turning off or turning on similar receptors) would be an asset in long term pain management. And of course we in medicine want to do it in a way that doesn't destroy nerve pathways - the way that leprosy works - and instead
Karmudjun
detach the person from whatever degree of pain they find intolerable. In the USA, human trials would determine the risk of a 'raised pain threshold' when a noninvasive technique becomes available - but no one I know would be willing to have the amount of surgery necessary to test this system in OUR central amygdala. That would require a significant pain level before I'd want even the most skilled stereotactic neurosurgeon implanting an optogenetic probe in my skull.
ljaques
I'm with Guz, anxiously awaiting fruition of this research. It could help SO many people!