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Targeting emotional aspects of pain could reduce opioid dependency

At the American Pain Society Annual Meeting, a plenary session speaker asked: "What if it were possible to develop a pain medication that could curb the negative emotions experienced by patients with chronic pain without causing euphoria and downstream addiction?"

April 8, 2019  By American Pain Society

The audience pondered the question as Jose Moron-Concepcion, Ph.D., associate professor of anesthesiology, neuroscience and psychiatry at Washington University School of Medicine in St. Louis, began his address. “We’re in the midst of an opioid epidemic, and the euphoria associated with opioids is a major driver of opioid dependence. By targeting the emotional aspects of pain, we hope to make pain less debilitating so patients won’t crave the emotional high from opioids,” Moron-Conception explained.

He added that chronic pain often brings sadness, depression and lethargy. That’s why opioids can be so addictive. Not only do they lessen the pain but often make patients feel euphoric. Thus, the trail toward addiction begins.

“Current pharmacological treatments focus mainly on the nociceptive component of pain, leaving the severe emotional disturbances understudied and poorly treated,” said Moron-Concepcion. “As the U.S. opioid epidemic continues to worsen, it is critical that we determine the factors and neural circuits contributing to this severe public health crisis.”

Moron-Concepcion reviewed animal research his team conducted and published in the journal Neuron. They explored if chemically blocking receptors in the brain linked with negative emotions could help restore a positive affect and improve motivation. In rats, researchers injected a paw with a substance that causes persistent inflammation, which results in the activation of kappa opioid receptors (KOR) that impedes motivation.

“When the animals experienced pain, they were less likely to seek a reward by pushing a lever to get a sugar pellet,” said Moron-Concepcion. “This is analogous to humans because people in pain don’t get as much pleasure from daily activities they normally enjoy.”


He reported that rats with inflamed paws were treated with a compound to block the endogenous KOR ligand, called dynorphin, in their brains. Quickly, the rats showed renewed motivation to seek the sugar pellets. PET scans showed that when rats were in pain their kappa receptors were very active in a brain region linked with emotion and motivation. “By blocking dynorphin release, motivation was restored even though the animals’ sensory component of pain was not eliminated,” said Moron-Concepcion.

Although the research is encouraging for perhaps finding a new approach to treat pain which could lower the addiction potential of opioids, Moron-Concepcion cautioned that many more studies are needed. He said PET scan data for humans is available, so it might be possible to conduct human trials to manipulate kappa opioid receptors and prevent the negative emotion and poor motivation that often come with physical pain.

“The data demonstrate that the dynorphin-KOR system in the brain represents an important target for new therapeutic approaches for treating pain-induced negative affect. By attacking the emotional aspects of pain, it could be possible to improve quality of life for pain patients without relying on as many addiction-prone opioid medications,” Moron-Conception said.

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