Pain “off” switch discovered in the brain

The quest to find a simple “off” switch for pain must rank as a major contender for the Holy Grail of neuroscience. But pain is deeply complex, particularly when it becomes established (referred to as “chronic pain”).

In January, we reported how scientists have revealed that gene-therapy might change the lives of people suffering chronic pain. Using a gene-editing tool, they believe they can make selective changes to an individual’s DNA to repress a gene responsible for sending pain signals through the nervous system. Though quietly promising, this process involves complex rewiring at the genetic level, rather than the simple flicking of a virtual switch.

Duke University study

Now, a research team at Duke University in the US has discovered a small area of the brain in mice that they believe acutely controls a mouse’s sense of pain. To their surprise, this tiny area turns pain off, not on.

“People do believe there is a central place to relieve pain, that’s why placebos work,” said lead author, Professor Fan Wang. “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,” she said. “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.”

One reason why this centre has only now been discovered is that it is located in an unexpected place, the amygdala, an area which is known to be linked to the experience of negative emotions and responses such as anxiety and our hard-wired fight or flight response. The researchers were surprised to discover that this tiny area, which they have named the “CeAga neurons”, is connected to many different areas of the brain.

Why are they looking at the brains of mice?

Believe it or not, the architecture of the human and mouse brain is very similar. Even viewed through a high-quality microscope, at first glance a neuroscientist might struggle to confirm whether a brain tissue sample belonged to a mouse or a human. Compared to humans, mice have a relatively large, central amygdala – humans have two, one in each temporal lobe – but the researchers believe we are likely to have a similar system for controlling pain.

What is the next step?

While the researchers have found that general anaesthesia activates the CeAga neurons’ “pain off” process, clearly that does not provide a practical, everyday application for their discovery! They are therefore searching for a drug that activates only those cells. Interestingly, they have also discovered that low-dose ketamine, a sometimes-controversial anaesthetic drug that allows sensation but blocks pain, activates the CeAga neurons, and that the activity of those cells is necessary for ketamine to work.

The possibilities presented by the discovery of the CeAga neurons, combined with the huge market potential for an effective pain-switch drug, will not have gone unnoticed in the pharma-industry. Their deep pockets and expertise may well help to fast-track the necessary research. In reality though, even if swift progress is made, it is likely to be some years before any drug comes to market.