Blocking a type of opioid receptor restores motivation — ScienceDaily

Chronic pain is more than just hurt. People with pain often feel sad, depressed and lethargic. This is one reason why opioids are so addictive – they not only reduce pain but also make people feel euphoric.

What if it is possible to develop a painkiller that can contain negative emotions associated with pain without causing euphoria? Researchers at the University of Washington's St. Louis Medical School have taken a step toward this goal. Studying rodents, they have shown that they block receptors in the brain, are responsible for the emotional components of pain and restore the animal's motivation. Their findings can lay the foundation for the development of new, less addictive pain treatments.

"We are in the epidemic of opioids, and excitement associated with opioids is a major driver of opioid dependence," said senior researcher Dr. Jose Moron-Concepcion, associate professor of anesthesiology, neuroscience and psychosis. learn. “By the emotional aspects of pain, we want to alleviate the pain so that patients don’t want to get emotionally high from opioids.”

Opioid painkillers such as morphine, oxycodone and fentanyl, target receptors on brain cells are called mu opioid receptors. In contrast, researchers at the University of Washington studied kappa opioid receptors, which operate in very different ways. Activating kappa receptors makes people feel depressed, sad and unmotivated. Therefore, Moron-Concepcion and his colleagues at the University of Washington Pain Center believe that by blocking these receptors, they may also suppress negative emotions associated with pain.

Their findings were published in the March 13 issue of the journal Neuron .

Some rats in the study injected paws with substances that cause persistent inflammation. To measure the emotional effects of this pain, the researchers used a useful task in which animals could use sugar as a measure of motivation. Most mice will continue to push after being taught to push the lever to get sugar. In these experiments, whenever they want a sucrose, the animal must gradually push the lever.

"When animals experience pain, they have no incentive to get rewards," said lead author Dr. Nicolas Massaly, an anesthesologist. “People who are suffering usually get as much fun as possible from the everyday activities they usually like.”

However, when an inflamed rat is treated with a compound to treat the kappa opioid receptor in the brain, the animal restores the motility to obtain sugar and pushes the lever as frequently as without the inflamed paw.

In addition, the researchers collaborated with Dr. Kooresh Shoghi, associate professor of radiology, to evaluate the activity of kappa opioid receptors in animal brains using small animal positron emission tomography (PET) imaging. They can prove that when the mice are in pain, their kappa opioid receptors are very active in the part of the brain, the nucleus accumbens, and are related to emotions.

The researchers inhibited this κ opioid receptor activity by blocking the release of a natural stimulator of a kappa opioid receptor called dynorphin – this is produced in the brain, a bit like the release of activity such as exercise. Reversal of endorphins.

"By blocking dynorphin release, we were able to restore animal motility, despite the fact that we did not completely eliminate their pain," Massaly said.

Moron-Concepcion, Massaly and their colleagues admit that this is a long journey from rodents to humans. But they have already obtained preliminary PET data from people, suggesting that it may affect kappa opioid receptors and may prevent grief and lack of motivation associated with body pain. They believe that by attacking the emotional characteristics of pain, without compromising the useful elements that can protect the injury from further damage, it can improve the quality of life of patients with pain without having to use any or as many habits as possible – formation Opioid painkillers.

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