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New Drug Therapy May End Chronic Pain

  • Published: 2015-12-28 : Author: Northwestern University : Contact:
  • Synopsis: The new treatment combines two FDA-approved drugs: a Parkinson's drug, L-dopa, and a non-steroidal anti-inflammatory drug.

Pain is a feeling triggered in the nervous system. Pain may be sharp or dull. It may come and go, or it may be constant. Pain is mediated by specific nerve fibers that carry the pain impulses to the brain where their conscious appreciation may be modified by many factors. Pain can be helpful in diagnosing a problem. Without pain, you might seriously hurt yourself without knowing it, or you might not realize you have a medical problem that needs treatment. Once you take care of the problem, pain usually goes away. However, sometimes pain goes on for weeks, months or even years. This is called chronic pain. Sometimes chronic pain is due to an ongoing cause, such as cancer or arthritis.

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"It was surprising to us that chronic pain actually rewires the part of the brain controlling whether you feel happy or sad..."

A brain region controlling whether we feel happy or sad, as well as addiction, is remodeled by chronic pain, reports a new Northwestern Medicine study, published in Nature Neuroscience.

And in a significant breakthrough for the millions of Americans suffering from chronic pain, scientists have 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 said.

"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, PhD, chair and Nathan Smith Davis Professor of Physiology. "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 study shows you can think of chronic pain as the brain getting addicted to pain," said A. Vania Apkarian, PhD, 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 showed. It went on to show 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 said.

In addition, Northwestern 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," said Marco Martina, MD, PhD, associate professor of Physiology and also a corresponding author.

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," Surmeier said.

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.

Chronic pain is an intractable problem for millions of Americans.

It's the number one cause of disability in the U.S. and costs more than $600 billion per year in in health care.

An estimated 20 percent of the U.S. and world population suffers from chronic pain, reports the World Health Organization and the National Academy of Sciences.

Other Northwestern authors include Jyothisri Kondapalli, PhD, research assistant professor of Physiology. Wenjie Ren. PhD, Maria Virginia Centeno and Sara Berger. This work was supported by grant DE022746 from the National Institute of Dental Research and grants NS064091 and NS 34696 from National Institute of Neurological Disorders and Stroke, of the National Institutes of Health.

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