Breakthrough research suggests simple ways to reverse chronic pain

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People who suffer from chronic pain often feel like the experience dominates their lives, and changes them profoundly. Now, a group of pain researchers and geneticists have discovered that this feeling isn't far from scientific truth. Being in chronic pain changes the way your brain functions on a physical level. The good news is that you can also change it back.

Pain researcher Maral Tajerian and her colleague Sebastian Alvarado wanted to find out whether chronic pain was changing the way the brain functions on a genetic level. Alvarado specializes in a burgeoning field called epigenetics, which looks at the way environment and experience affect gene expression, or activity. Was chronic pain epigenetic, an experience that changed brain gene function? They quickly discovered the answer was a resounding yes.

Tajerian and Alvarado's work centered on mice who suffered a nerve injury that put them in chronic pain. Over a period of months, they discovered that the pain was affecting regions of the mice's brains that had nothing to do with processing pain. In fact, they found that gene activity had been severely curtailed in the prefrontal cortex, a brain area that serves as the seat of higher reason and decision-making, as well as many emotions, in both rodents and humans.


"We saw chemical changes to the DNA in [the prefrontal cortex]," Alvarado told io9. Specifically, they found a 12 percent downward shift in DNA activity. "That's really big," he added. "Normally these changes are associated with cancer." This lack of activity, Tajerian said, leads to a loss of density in this region of the brain — which ultimately causes cognitive impairment, depression and anxiety.

Taking the "Chronic" Out of Pain

If pain could change brain activity, Tajerian and Alvarado wondered, were there activities that could change it back? The two worked with colleagues at McGill University to design a simple experiment that might answer this question. They created groups of mice who had all suffered injuries that would cause long-term pain. One group was subjected to "impoverishment," which meant a very small cage where they lived alone. Another group enjoyed "enrichment," which meant they had a roomy cage with other mouse friends, as well as marbles to play with. Both groups had the same amount of food and care otherwise. (There was also a control that got typical lab mouse treatment.)

After two months, the mice in the enriched environment did not suffer chronic pain any longer. Or rather, their prefrontal cortexes showed normal mouse activity. Meanwhile, the impoverished mice showed the reduction in brain activity, which led to cognitive impairment. Along with colleagues, the two published a paper in PLoS One about the study earlier this year. The paper provides strong evidence that chronic pain is an epigenetic phenomenon, a life experience that actually changes gene expression in the brain.

Translated into human terms, this means that some people experience chronic pain because they have literally rewired their brains to be more sensitive to pain. The more pain they feel, the more anxious and vulnerable they are to feeling further pain.


And that's actually a good thing.

"This paper gives me hope," said Tajerian. The brain is a much more plastic organ than scientists realized even a decade ago, and the actions we take today can actually change how our brains function tomorrow. "A different environment will give you a different experience of pain. By changing the environment we could change the pain," she said. "Having fun and friends is really good for you."


Tajerian and Alvarado caution that what the enriched mice experienced wasn't an end to pain from their injuries. Instead, it was more like the pain didn't bother them as much. Put another way, their fun, social environment took the chronic out their pain.

A Reversible Mechanism

So what is happening to the brains of people with chronic pain? First of all, they are experiencing a measurable, biological phenomenon — it's not just "in their minds;" it's in their genes. There is a tremendous amount of variety in their experiences, too. If you have two people with the same injury, one may develop chronic pain and the other may not. This could be the result of a genetic predisposition, environment, or both.


Tajerian and Alvarado's work shows, as Tajerian puts it, "you are a different person" after an injury. But that person can change again, into somebody who "cares about the pain less." She suggests that their discoveries help illuminate why meditation and mindfulness can help with pain. "Even cursing can help you care about the pain less," she laughed. These activities are all ways of changing our environment, and our brains, by making us calmer or allowing us to express feelings.

There is one particular chemical switch that gets thrown in the prefrontal cortex during chronic pain. It's called DNA methylation. Molecules from a methyl group attach themselves to genes, and inhibit those genes' expression or activity. DNA that's methylated is switched off. Chronic pain causes a 12 percent rise in DNA methylation in the prefrontal cortexes of mice.


Tajerian said:

The analogy we use is a city at night. You can see how many buildings are lit, and how many are in the dark. You can take a picture and say 20 percent are lit, versus another time when it's 15 percent. That's what we're seeing with methylation, which is a switch that turns the lights off. So if a regular brain has a certain amount of lights, one with chronic pain has 12 percent less.


And that is a tremendous change. But, as the enriched mice demonstrate, it's also a state that can be changed back. The lights can go back on, at a molecular level. The mice who lived in an enriched environment managed to relight those darkened windows in two months.

"It's a reversible mechanism," Alvarado asserted. In a forthcoming paper, Alvarado will present research he's done on which genes are methylated during chronic pain, and many of those genes have to do with neural growth and neurotransmission. This might mean that chronic pain prevents the brain from changing and processing new information.


It also means that creating the human equivalent of an enriched environment could train your brain to reinterpret your pain. What this research also reveals is that there is actually a molecular mechanism that demonstrates that it's good to have company — or at least, to have some really fun videogames to make you feel better when you've been hurt.

You can read the full scientific paper on PLoS One. This research was conducted in the labs of Dr. Laura Stone and Dr. Moshe Szyf.


Illustration by Melodia plus photos via Shutterstock