Wed. Dec 2nd, 2020

A 'switch' in the brain that shuts down pain discovered by scientists

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A ‘switch’ in the brain that shuts down pain has been discovered.

Scientists have found a small area of the brain in mice that can ‘profoundly’ control the animals’ sense of pain.

They said the brain centre that turns pain off, not on, is located in an area where few people would have thought to look for an anti-pain centre, the amygdala, which is often considered the home of negative emotions and responses, such as the ‘fight or flight’ response and general anxiety.

Study senior author Professor Fan Wang, of Duke University in the United States, said: ‘People do believe there is a central place to relieve pain, that’s why placebos work.

‘The question is where in the brain is the centre 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 centre can turn off the pain by itself.”

The latest study is a follow-up to earlier research in Prof Wang’s lab looking at neurons that are activated, rather than suppressed, by general anaesthetics.

In a 2019 study, the team found that general anaesthesia promotes slow-wave sleep by activating the supraoptic nucleus of the brain.

But sleep and pain are separate – an important clue that led to the new finding, published online in the journal Nature Neuroscience.

The researchers found that general anaesthesia also activates a specific subset of inhibitory neurons in the central amygdala, which they have called the CeAga neurons.

Mice have a relatively larger central amygdala than humans, but Prof Wang said she had no reason to think that man has a different system for controlling pain.

Using technologies that Prof Wang’s lab has pioneered to track the paths of activated neurons in mice, the team found the CeAga was connected to many different areas of the brain – a finding Prof Wang described as ‘a surprise..’

By giving mice a mild pain stimulus, the researchers could map all of the pain-activated brain regions.

They found that at least 16 brain centres known to process the sensory or emotional aspects of pain were receiving inhibitory input from the CeAga.

Prof Wang said: “Pain is a complicated brain response. It involves sensory discrimination, emotion, and autonomic 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.’

Using a technology called optogenetics, which uses light to activate a small population of cells in the brain, the researchers found they could turn off the self-caring behaviours a mouse exhibits when it feels uncomfortable by activating the CeAga neurons.

Paw-licking or face-wiping behaviours were ‘completely abolished’ the moment the light was switched on to activate the anti-pain centre.

Prof Wang said: ‘It’s so drastic. They just instantaneously stop licking and rubbing.”

They also found that low-dose ketamine, an anaesthetic drug that allows sensation but blocks pain, activated the CeAga centre and wouldn’t work without it.

Now the researchers are going to look for drugs that can activate only those cells to suppress pain as potential future pain killers.

Prof Wang added: ‘The other thing we’re trying to do is to sequence the hell out of these cells.’

The researchers are hoping to find the gene for a rare or unique cell surface receptor among these specialised cells that would enable a very specific drug to activate these neurons and relieve pain.

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