Chronic pain affects more than 50 million Americans and remains one of the most difficult conditions to treat safely and effectively. While opioids have long been a cornerstone of pain management, their use comes at a steep cost—addiction, constipation, tolerance, withdrawal, and a staggering impact on public health. But a study published in Cell explores a new small molecule called SBI-810, a compound that may provide the pain-relieving benefits of opioids without their debilitating side effects.
SBI-810 is a β-arrestin-biased positive allosteric modulator (PAM) of the neurotensin receptor 1 (NTSR1), a receptor system distinct from the classical opioid pathway. In a series of rigorous experiments, researchers found that SBI-810 not only reduces pain across multiple preclinical models but also reduces morphine-induced reward, dependence, and side effects like constipation.
Perhaps most intriguing is SBI-810’s ability to relieve pain independently. The compound demonstrated robust analgesia in models of postoperative, inflammatory, and neuropathic pain, with efficacy seen in both central and peripheral pathways. Mechanistically, SBI-810 dampened excitatory synaptic transmission in spinal neurons and decreased Nav1.7 sodium channel surface expression in dorsal root ganglion (DRG) neurons—two crucial mediators of pain hypersensitivity.
“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.
Safety is another major advantage. SBI-810 produced no impairments in motor coordination, cognition, or tactile sensitivity. It also significantly mitigated morphine-induced constipation, a pervasive issue in long-term opioid therapy. In gastrointestinal transit assays, SBI-810-treated animals showed a marked improvement in gut motility compared to those treated with morphine alone.
SBI-810 is still in preclinical development, but its unique mechanism of action and favorable safety profile mark it as a promising candidate in the search for non-addictive pain therapies. By bypassing the opioid system while retaining potent analgesia, this compound may herald a new era in pain management—one that treats suffering without trading it for dependence.
Sources: EurekAlert, Cell
