The drug, called SBI-810, 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, a non-opioid treatment, 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 published May 19 in Cell.

“What makes this compound exciting is that it is both analgesic and non-opioid,” said senior study author Ru-Rong Ji, PhD, an anesthesiology and neurobiology researcher who directs the Duke 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 Duke researchers are aiming for human trials soon and they’ve locked in multiple patents for the discovery.

There’s an urgent need for pain relief alternatives. 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 U.S. population.

Researchers said 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 said. “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.

Duke scientists 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.

Researchers said 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.

The study was supported by the NIH and the Department of Defense.

Additional Duke authors include first authors Ran Guo and Ouyang Chen; Sangsu Bang, Sharat Chandra, Yize Li, Gang Chen, Rou-Gang Xie, Wei He, Jing Xu, Richard Zhou, Shaoyong Song, Ivan Spasojevic, Marc G. Caron, William C. Wetsel and Lawrence S. Barak.??