A promising experimental drug developed at Duke University School of Medicine, known as SBI-810, may soon offer potent pain relief without the dangerous side effects and addictive potential associated with traditional opioids. This non-opioid treatment represents a new generation of compounds targeting specific nerve receptors, offering a more focused approach to pain management.
The findings, published on May 19 in the journal Cell, indicate that SBI-810 not only works effectively on its own in mice but can also enhance the efficacy of opioids at lower doses when used in combination.
The Urgent Need for Opioid Alternatives
The development of safer pain relief options is a pressing global health priority. While drug overdose deaths are seeing some decline, over 80,000 Americans still die annually, predominantly from opioids. Furthermore, chronic pain impacts roughly one-third of the U.S. population, highlighting the vast number of individuals who could benefit from safer, long-term pain management solutions. Researchers believe SBI-810 could become a vital option for treating both acute pain (e.g., post-surgery) and chronic conditions like diabetic nerve pain.
How SBI-810 Works: A Targeted Approach with Biased Agonism
Unlike opioids that broadly activate multiple cellular pathways, leading to the desired pain relief but also the euphoric “high” linked to addiction and other side effects, SBI-810 employs a sophisticated mechanism called biased agonism.
Biased Agonism describes a phenomenon where a specific agonist (a “biased key”) can bind to a receptor and preferentially activate only some of the available downstream signaling pathways, while having less effect on (or even inhibiting) other pathways that the same receptor could normally trigger with a different (non-biased or “balanced”) agonist.
“What makes this compound exciting is that it is both analgesic and non-opioid,” said senior study author Ru-Rong Ji, Ph.D., an anesthesiology and neurobiology researcher who directs the Duke Anesthesiology Center for Translational Pain Medicine.
SBI-810 specifically targets the neurotensin receptor 1, found on sensory neurons and in the brain and spinal cord. Using biased agonism, it selectively activates the β-arrestin-2 signaling pathway, which is linked to pain relief, while avoiding other signals that can trigger unwanted side effects or lead to addiction.
Promising Pre-clinical Results in Mice
In pre-clinical studies involving mice, SBI-810 demonstrated significant efficacy:
- It effectively relieved pain from surgical incisions, bone fractures, and nerve injuries, in some cases better than existing painkillers.
- The drug reduced signs of spontaneous discomfort, such as guarding behavior and facial grimacing.
- When compared to oliceridine (a newer type of opioid used in hospitals), SBI-810 performed better in certain pain scenarios with fewer signs of distress in the animal models.
- Crucially, unlike opioids such as morphine, SBI-810 did not cause tolerance after repeated use, meaning dosage did not need to be progressively increased.
- It also outperformed gabapentin, a common medication for nerve pain, and did not cause sedation or memory problems often associated with gabapentin.
- Common opioid-induced side effects like constipation were also avoided.
Future Outlook: Towards Human Trials
While SBI-810 is still in the early stages of development, Duke researchers are optimistic and aiming for human trials in the near future. They have secured multiple patents for this discovery. The compound’s dual action on both peripheral and central nervous systems suggests it could strike a new balance in pain medicine: delivering powerful relief while being specific enough to minimize harm.
