Researchers at Duke University School of Medicine have developed an experimental drug, SBI-810, that could provide powerful pain relief without the addictive side effects of opioids.

Published in Cell, the study reveals that SBI-810 targets pain at its source—blocking discomfort without triggering euphoria, tolerance, or dangerous side effects like respiratory depression. If successful in human trials, this drug could revolutionize pain management for post-surgical recovery, chronic nerve pain, and injuries.

Here’s how it works, why it’s different from opioids, and what it could mean for the future of pain treatment.

About the research

1. Targeting the Right Receptor Without the Risks

Unlike opioids, which broadly affect the brain’s reward and respiratory systems, SBI-810 zeroes in on the neurotensin receptor 1 (NTSR1)—a protein found in sensory nerves, the spinal cord, and brain regions linked to pain processing.

Using biased agonism, the drug activates only the β-arrestin-2 pathway, which blocks pain signals while avoiding pathways that cause addiction or side effects.

“It’s both analgesic and non-opioid—that’s what makes it exciting,” says Dr. Ru-Rong Ji, lead researcher at Duke’s Anesthesiology Center for Translational Pain Medicine.

2. Outperforming Existing Painkillers in Mice

In preclinical trials, SBI-810:

• Relieved post-surgical pain better than some opioids.
• Reduced nerve pain more effectively than gabapentin (a common nerve pain drug).
• Prevented tolerance—unlike morphine, which loses effectiveness over time.
• Avoided sedation, constipation, and respiratory depression—common opioid side effects.

Mice given SBI-810 showed fewer signs of discomfort (e.g., limb guarding, facial grimacing) without behavioral side effects.

Why This Matters

1. Addressing the Urgent Need for Safer Alternatives

With opioid-related overdoses claiming more than 80,000 American lives each year and chronic pain affecting approximately one-third of the U.S. population, the demand for safer pain management options has never been greater. Current alternatives like gabapentin and NSAIDs come with their own limitations, including sedation and gastrointestinal risks. SBI-810 represents a promising middle ground by offering potent pain relief without the inherent risks of addiction associated with opioids.

2. Broad Implications for Future Medical Research

The success of SBI-810’s biased agonism approach could pave the way for developing new generations of non-addictive medications. Furthermore, the neurotensin receptors targeted by this drug may also play significant roles in conditions such as migraines, inflammation, and mood disorders, potentially opening new avenues for treating these conditions in the future.

3. Transforming Post-Surgical Recovery

SBI-810 could revolutionize post-operative care by either replacing or significantly reducing the need for opioid prescriptions. Its ability to prevent tolerance development means patients could maintain consistent, effective dosing without the risk of escalating dependency.

4. Improving Chronic Pain Management

Patients suffering from chronic conditions like diabetic neuropathy, sciatica, fibromyalgia, and arthritis pain might find relief through SBI-810’s targeted action. Unlike current treatments, this drug appears to avoid the cognitive impairment and sedation associated with long-term pain management regimens.

5. Advancing Trauma and Emergency Medicine

The compound shows particular promise for treating acute pain from bone fractures, burns, and nerve injuries without the sedation risks that complicate recovery in emergency situations.

6. Supporting Military and Veteran Health

The country’s Department of Defense is involved in funding. This research suggests potential applications in battlefield medicine, where effective pain management without impairment is crucial for both immediate care and long-term veteran health.

SBI-810 represents a significant advancement in pain management, potentially ushering in an era where effective relief doesn’t come with the risk of addiction. Several important factors must be addressed before the pain killler can become widely available. The drug has not yet been tested in humans, and results from animal studies don’t always translate perfectly to human biology. While no tolerance was observed in mice during the study period, the long-term effects in humans remain unknown.