Experimental Painkiller Outperforms Opioids, Avoids Side Effects

Researchers at Duke University School of Medicine have developed an experimental compound that could deliver effective pain relief while avoiding the adverse effects associated with opioids. The compound, SBI-810, is designed to activate a specific pain-relief mechanism in the nervous system without triggering pathways linked to addiction and other opioid-related complications.

The findings were published May 19 in Cell and are based on animal studies showing SBI-810 reduces pain responses in various preclinical models.

Specific receptor pathway offers focused pain relief

Unlike opioids, which broadly affect multiple cellular signals, SBI-810 selectively activates neurotensin receptor 1, a protein found on sensory neurons and in regions of the brain and spinal cord associated with pain processing. The compound uses a pharmacological strategy known as biased agonism to stimulate the β-arrestin-2 signaling pathway. This pathway has been linked to analgesia without the adverse effects commonly seen with opioid medications.

In studies involving mice, SBI-810 reduced signs of acute and chronic pain, including responses following surgical incisions, fractures and nerve injuries. It also improved opioid efficacy when co-administered, enabling lower doses of opioids to be used for the same level of pain relief.

“What makes this compound exciting is that it is both analgesic and non-opioid,” said Dr. Ru-Rong Ji.

Fewer side effects compared with current therapies

The researchers found that SBI-810 did not induce common opioid-related side effects such as constipation or tolerance, the latter of which often leads to escalating doses in patients. The compound also outperformed gabapentin, a standard treatment for nerve-related pain, in tests assessing behavioral signs of discomfort, and did not cause sedation or cognitive impairment.

When tested against oliceridine, a recently approved opioid used in clinical settings, SBI-810 performed as well or better in some models and produced fewer observable signs of distress in mice.

“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.”

Path to further development

While SBI-810 remains in the early stages of development, the research team has secured several patents related to the compound and its mechanisms. Plans are in place to move toward human clinical trials. If successful, the drug may become part of a new class of non-opioid analgesics suitable for treating both postoperative and neuropathic pain.

Chronic pain remains a widespread condition, affecting around one-third of the US population. Although overdose deaths from opioids have started to decline, opioids continue to be a leading cause of drug-related mortality, with more than 80,000 deaths annually in the United States.

Reference: Guo R, Chen O, Zhou Y, et al. Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain. Cell. 2025:S0092867425005082. doi: 10.1016/j.cell.2025.04.038

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