Researchers Say Chronic Pain Rewires Brain

By Pat Anson, Editor

Researchers at Northwestern University say a brain region that controls whether we feel happy or sad is rewired by chronic pain.

Their research on laboratory rats, published in the journal Nature Neuroscience, may have also uncovered a new treatment strategy that restores the brain and dramatically lessens pain.

'It was surprising to us that chronic pain actually rewires the part of the brain controlling whether you feel happy or sad," said corresponding author D. James Surmeier, chair of physiology at Northwestern University Feinberg School of Medicine. "By understanding what was causing these changes, we were able to design a corrective therapy that worked remarkably well in the models. The question now is whether it will work in humans."

The new treatment combines a Parkinson's drug, L-dopa, and a non-steroidal anti-inflammatory drug (NSAID), both of which are FDA approved. The combined drugs target brain circuits in the nucleus accumbens and completely eliminated chronic pain behavior when administered to rodents. The key is administering the drugs together and soon after an injury.

The scientists hope to begin a clinical trial on humans to further test their theory.

"The study shows you can think of chronic pain as the brain getting addicted to pain," said A. Vania Apkarian, a professor of physiology at Feinberg. "The brain circuit that has to do with addiction has gotten involved in the pain process itself."

The researchers found that a group of neurons thought to be responsible for negative emotions became hyper-excitable within days after an injury that triggers chronic pain. This change was triggered by a drop in dopamine, a neurotransmitter.

"These results establish chronic pain cannot be viewed as a purely sensory phenomenon but instead is closely related to emotions," Apkarian said.

When scientists gave the rats the NSAID and L-dopa, which raises dopamine levels, the changes in the brain were reversed and the animals' chronic pain behavior stopped. That suggests supplementing anti-inflammatories with a medication that activates dopamine receptors or raises dopamine levels might be an effective way of treating chronic pain or preventing the transition from acute to chronic pain.

Scientists also treated the rats with another Parkinson's drug, pramipexole, which activates dopamine receptors and mimics dopamine's effect. That drug also decreased the animals' pain-like behavior.

"It is remarkable that by changing the activity of a single cell type in an emotional area of the brain, we can prevent the pain behavior," said Marco Martina, an associate professor of physiology at Feinberg.

In addition to Parkinson’s, L-Dopa is used to combat anxiety and depression, and to improve the ability to concentrate and focus. L-Dopa is sold under the brand names Levodopa, Sinemet, Madopar, Stalevo, and Prolopa.

A recent study by British researchers also found that brain chemistry is changed by chronic pain.

Researchers at the University of Manchester used PET scans to measure the spread of opioid receptors in the brains of 17 arthritis sufferers and nine healthy control subjects. The number of opioid receptors was highest in the arthritis sufferers, suggesting their brain chemistry had changed and made them more resilient to pain. That could explain why some people are better able to cope with pain than others.

The University of Manchester study is being published in Pain, the official journal of the International Association of the Study of Pain.