ANN ARBOR, Mich. — Opioids, such as oxycodone, fentanyl, and morphine, are well-known for their pain relieving powers. Although they are potent pain reducers, they can also be very addicting, which can lead to overdoses and death. Over the years, scientists have struggled to find a way to balance the effectiveness of prescription painkillers while eliminating the many detrimental side-effects they cause. Now, researchers from the University Michigan find boosting the body’s innate capacity to inhibit pain may help remove the need to use addictive opioids.
“Normally, when you are in pain, you are releasing endogenous opioids, but they’re just not strong enough or long-lasting enough,” says John Traynor in a university release.
Opioid receptors found naturally in the brain and throughout the body interact with all narcotics, from codeine to heroin. The common receptor for these interactions is the “mu-opioid receptor,” which attaches to endorphins — the body’s biological pain killers. Addiction and unpleasant side-effects including sleepiness, breathing difficulties, incontinence, and nausea can result from using drugs that affect this receptor or the binding site.
“When you need enkephalins, you release them in a pulsatile fashion in specific regions of the body, then they are metabolized quickly,” explains Traynor. “In contrast, a drug like morphine floods the body and brain and sticks around for several hours.”
One chemical can help boost pain management
Researchers believe they can enhance these naturally occurring pain relievers using chemicals known as positive allosteric modulators (PAMs). One specific PAM, BMS-986122, improves the capability of enkephalins (which are similar to endorphins) to trigger the mu-opioid receptor.
The PAMs only act in the context of endorphins or other natural painkillers, which means they are only activate when the body needs pain relief. Since they don’t directly connect to opioid receptors, they boost the body’s capacity to react to pain-relieving chemicals by attaching to different areas.
When researchers extracted and assessed the mu-opioid receptor to measure its response to enkephalins, they found that the regulator had the capacity to activate the receptor and increase its activity.
“If you add the positive allosteric modulator (PAM), you need a lot less enkephalin to get the response,” Traynor adds.
Opioid receptors were more responsive to pain-relieving chemicals, which the team demonstrated through electrophysiological studies and experiments with mice. The regulator, on the other hand, had fewer adverse effects, including respiratory failure, incontinence, and addiction risk.
“While these molecules won’t solve the opioid crisis,” Traynor concludes, “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.”
According to the Michigan team, the team’s next objective is to evaluate their potential to increase the stimulation of naturally derived painkillers, such as endorphins, under stressful or persistent pain settings in order to guarantee their efficacy.
These findings are published in the journal Proceedings of the National Academy of Sciences.