New Non-Opioid Drug Offers Powerful Pain Relief Without the Dangerous Side Effects

The compound provides non-opioid pain relief by targeting neurotensin receptor 1 (NTSR1) on sensory neurons and within the spinal cord.

Scientists at Duke University School of Medicine have developed a promising new drug that could deliver strong pain relief without the dangerous side effects linked to opioids.

The compound, known as SBI-810, belongs to a new class of medicines that work in a smarter, more targeted way. Unlike opioids, which affect many pathways throughout the body and often trigger addiction and side effects, SBI-810 zeroes in on a single pain-relief signal in the nervous system. This focused action avoids the euphoric “high” that can lead to misuse and dependency.

In early lab tests with mice, SBI-810 proved highly effective. On its own, it eased pain significantly. When paired with small doses of opioids, it boosted their effectiveness, allowing for much lower opioid use overall. These results were published in the journal 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.

Moving Toward Human Trials

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.”

Outperforming Current Treatments

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.

Reference: “Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain” by Ran Guo, Ouyang Chen, Yang Zhou, Sangsu Bang, Sharat Chandra, Yize Li, Gang Chen, Rou-Gang Xie, Wei He, Jing Xu, Richard Zhou, Shaoyong Song, Kelsey L. Person, Madelyn N. Moore, Abigail R. Alwin, Ivan Spasojevic, Michael R. Jackson, Steven H. Olson, Marc G. Caron, Lauren M. Slosky, William C. Wetsel, Lawrence S. Barak and Ru-Rong Ji, 19 May 2025, Cell.
DOI: 10.1016/j.cell.2025.04.038

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

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