Irvine, Calif., June 9, 2015 — Brain inflammation caused by chronic nerve pain alters activity in regions that regulate mood and motivation, suggesting for the first time that a direct biophysical link exists between long-term pain and the depression, anxiety and substance abuse seen in more than half of these patients, UC Irvine and UCLA researchers report.

This breakthrough finding also points to new approaches for treating chronic pain, which is second only to bipolar disorder among illness-related causes of suicide. About a quarter of Americans suffer from chronic pain, making it the most common form of enduring illness for those under the age of 60. The Institute of Medicine estimates that this costs our society more than $635 billion per year.

In work with rodents, Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI; Christopher Evans of UCLA’s Brain Research Institute; and colleagues discovered that pain-derived brain inflammation causes the accelerated growth and activation of immune cells called microglia. These cells trigger chemical signals within neurons that restrict the release of dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers.

The study also reveals why opioid drugs such as morphine can be ineffective against chronic pain. Morphine and its derivatives normally stimulate the release of dopamine. But in research on mice and rats in chronic pain, Cahill and her colleagues learned that these drugs failed to stimulate a dopamine response, resulting in impaired reward-motivated behavior.

Treating these animals in chronic pain with a drug that inhibits microglial activation restored dopamine release and reward-motivated behavior, Cahill said.

“For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction,” she added. “Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders.”

The results of the five-year study appear online in The Journal of Neuroscience.

Next, Cahill and her team aim to establish that pain-derived changes in human brain circuitry can account for mood disorders. “We have a drug compound that has the potential to normalize reward-like behavior,” she said, “and subsequent clinical research could then employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients.”

Christopher Cook of UCI; Anna Taylor, Alison Taylor, Niall Murphy and Atefeh Ghogha of UCLA; Annie Castonguay and Yves De Koninck of Laval University in Quebec City; and Lihua Xue and Mary Olmstead of Queen’s University in Kingston, Ontario, Canada, also contributed to the study. The National Institutes of Health (DA005010), the Shirley & Stefan Hatos Neuroscience Research Foundation and the Canadian Institutes of Health Research (12942, 123298) provided support.

About the University of California, Irvine: Currently celebrating its 50th anniversary, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $4.8 billion annually to the local economy. For more on UCI, visit www.uci.edu.

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