Chronic pain remodels a brain region that controls whether we feel happy or sad, as well as addiction, a new study reports. The scientists have also developed a new treatment strategy that restores this region and dramatically lessens pain symptoms in an animal model.
The new treatment combines two FDA-approved drugs: a Parkinson’s drug, L-dopa, and a non-steroidal anti-inflammatory drug. The combined drugs target brain circuits in the nucleus accumbens and completely eliminate chronic pain behavior when administered to rodents with chronic pain. The key is administering the drugs together and shortly after an injury.
As a result of the study’s findings, the scientists are pursuing a clinical trial. The treatment has the potential to prevent chronic pain if used early enough after injury, the scientists say. Their work appears in Nature Neuroscience.
“It was surprising to us that chronic pain actually rewires the part of the brain controlling whether you feel happy or sad,” says 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.”
Chronic pain, which affects millions of Americans, is the number one cause of disability in the US and costs more than $600 billion per year in in health care.
“The study shows you can think of chronic pain as the brain getting addicted to pain,” says A. Vania Apkarian, also a corresponding author and a professor of physiology. “The brain circuit that has to do with addiction has gotten involved in the pain process itself.”
A group of neurons thought to be responsible for negative emotions became hyper-excitable and more strongly connected with other regions of the brain linked to feeling bad within days after an injury that triggers chronic pain behavior, the study shows. It also shows this change was triggered by a drop in dopamine, a critical neurotransmitter.
When scientists administered the non-steroidal anti-inflammatory drug and L-dopa, which raises dopamine levels, the changes in the brain were reversed and the animals’ chronic pain behavior stopped.
“These results establish chronic pain cannot be viewed as a purely sensory phenomenon but instead is closely related to emotions,” Apkarian says.
Aim at dopamine?
In addition, the scientists treated rats experiencing chronic pain with another Parkinson’s drug, pramipexole, that activated dopamine receptors, mimicking dopamine’s effect. This 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,” says Marco Martina, associate professor of physiology and also a corresponding author of the study.
Currently, the most common treatment for chronic pain is a non-steroidal anti-inflammatory type of drug, which has limited effectiveness.
“The treatments for chronic pain we currently have are very limited,” says Surmeier.
The results of the study suggest supplementing anti-inflammatories with a medication that activates dopamine receptors or raises dopamine levels might be more effective in treating chronic pain and/or preventing a transition to chronic pain.
Support for the work came from National Institute of Dental Research and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.
Source: Northwestern University