New painkiller could ditch dangerous opioid side effects

An experimental drug could offer powerful pain relief without the dangerous side effects of opioids.

Called SBI-810, the drug is part of a new generation of compounds designed to target a receptor on the nerves and spinal cord.

While opioids flood multiple cellular pathways indiscriminately, SBI-810 takes a more focused approach, activating only a specific pain-relief pathway that avoids the euphoric “high” linked to addiction.

In tests in mice, SBI-810 worked well on its own and, when used in combination, made opioids more effective at lower doses, according to the study in Cell.

“What makes this compound exciting is that it is both analgesic and non-opioid,” says senior study author Ru-Rong Ji, an anesthesiology and neurobiology researcher who directs the Duke University Anesthesiology Center for Translational Pain Medicine.

Even more encouraging: it prevented common side effects like constipation and buildup of tolerance, which often forces patients to need stronger and more frequent doses of opioids over time.

SBI-810 is in early development, but the researchers are aiming for human trials soon and have secured multiple patents for the discovery.

There’s an urgent need for non-opioid pain relievers. Drug overdose deaths are declining, but more than 80,000 Americans still die each year most often from opioids. Meanwhile, chronic pain affects one-third of the US population.

Researchers says the drug could be a safer option for treating both short-term and chronic pain for those recovering from surgery or living with diabetic nerve pain.

SBI-810 is designed to target the brain receptor neurotensin receptor 1. Using a method known as biased agonism, it switches on a specific signal—β-arrestin-2—linked to pain relief, while avoiding other signals that can cause side effects or addiction.

“The receptor is expressed on sensory neurons and the brain and spinal cord,” Ji says. “It’s a promising target for treating acute and chronic pain.”

SBI-810 effectively relieved pain from surgical incisions, bone fractures, and nerve injuries better than some existing painkillers. When injected in mice, it reduced signs of spontaneous discomfort, such as guarding and facial grimacing.

The researchers compared SBI-810 to oliceridine, a newer type of opioid used in hospitals, and found SBI-810 worked better in some situations, with fewer signs of distress.

Unlike opioids like morphine, SBI-810 didn’t cause tolerance after repeated use. It also outperformed gabapentin, a common drug for nerve pain, and didn’t cause sedation or memory problems, which are often seen with gabapentin.

The researchers say the compound’s dual action—on both the peripheral and central nervous systems—could offer a new kind of balance in pain medicine: powerful enough to work, yet specific enough to avoid harm.

Support for the study came from the National Institutes of Health and the Department of Defense.

Source: Duke University

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