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Scientists learn how to activate the body's natural pain killers

The body’s natural pain killers can be stimulated, according to a new study from Michigan Medicine. Experiments in both cells and mice revealed that pain-relieving compounds in the human body can be effectively enhanced with fewer side effects than opioids. 

Drugs like fentanyl, oxycodone, and morphine are known as a reliable source of pain relief, but are also known as the cause of widespread addiction and death.

For years, experts have tried to balance the pain-relieving properties of opioids with their numerous negative side effects without a lot of success. Led by Dr. John Traynor and Dr. Andrew Alt, the Michigan Medicine team has turned its attention to harnessing the body’s own ability to block pain.

All opioid drugs, from opium to heroin, work on receptors that are naturally present in the brain and elsewhere in the body. One receptor, the mu-opioid receptor, binds to natural pain killers in the body called endogenous endorphins and enkephalins. 

“Normally, when you are in pain, you are releasing endogenous opioids, but they’re just not strong enough or long lasting enough,” said Dr. Traynor. The team had long theorized that substances called positive allosteric modulators could be used to enhance the body’s endorphins and enkephalins. 

In their latest study, the researchers have demonstrated that a positive allosteric modulator known as BMS-986122 can boost the ability of enkephalins to activate the mu-opioid receptor.

Unlike opioid drugs, positive allosteric modulators only work in the presence of endorphins or enkephalins, meaning they would only kick in when needed for pain relief. 

The modulators bind to the receptor in a different location than opioids – one that enhances the receptor’s ability to respond to natural pain relief.

“When you need enkephalins, you release them in a pulsatile fashion in specific regions of the body, then they are metabolized quickly,” explained Dr. Traynor. “In contrast, a drug like morphine floods the body and brain and sticks around for several hours.”

The next goal is to enhance activation of endogenous opioids under conditions of stress or chronic pain, to ensure that they are effective but do not lead to more dangerous responses like depression of breathing, said Dr. Traynor.

“While these molecules won’t solve the opioid crisis, they could slow it and prevent it from happening again because patients in pain could take this type of a drug instead of a traditional opioid drug.”

The study is published in the journal Proceedings of the National Academy of Sciences.

By Chrissy Sexton, Staff Writer

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