New pain medications target neural receptors, bypassing addiction pathways

Duke University researchers have developed a promising new pain relief agent that works through a completely different mechanism than opioids, potentially providing alternatives to millions of chronic pain patients without the dangerous side effects of addiction and tolerance. The experimental drug called SBI-810 targets specific receptors in the nerves and spinal cord while avoiding reward pathways in the brain, making opioids so problematic.

The findings, published in cells on May 19, show that SBI-810 effectively treats acute pain (such as surgery or injury), as well as chronic pain for nerve damage in animal models. What makes this compound particularly exciting is its accuracy: instead of flooding the body with traditional painkillers (traditional painkillers), SBI-810 only activates specific cellular pathways associated with pain relief.

As the United States continues to cope with an opioid crisis, with more than 80,000 lives each year, and one-third of Americans suffer from chronic pain, the need for safer, more effective alternatives has never been more urgent. Can this targeted approach eventually break the cycle of addiction and ineffective treatment that has plagued pain management for decades?

Smarter ways to relieve pain

“What makes this compound exciting is that it is both a painkiller and a non-opioid,” said senior study author Ru-Rong Ji, PhD.

Unlike multiple cellular pathways where opioids indiscriminately activate the entire body and brain, SBI-810 targets a specific receptor called neurotin receptor 1 (NTSR1). This receptor is found on sensory neurons and the entire central nervous system, making it an ideal target for pain management.

The drug uses a complex method called a “biased agonist” to activate only specific cellular signals (β-arrestin-2), which relieves pain while avoiding other signals that may cause side effects or addiction.

“Receptors are expressed in sensory neurons, brain and spinal cord,” explains JI. “This is a promising goal for treating acute and chronic pain.”

Powerful results for multiple pain types

In laboratory tests, SBI-810 demonstrated significant versatility and effectiveness in treating various pains:

• Get rid of pain from surgical incisions, fractures and nerve damage
• Reduce signs of spontaneous discomfort, including protective behavior and facial ghosting
• Better than gabapentin, a common nerve pain medication
• In some pain models, better results than rugby (a newer hospital-grade opioid)
• Maintaining effectiveness through reuse, avoiding the tolerance problem that plagues opioid treatments

Perhaps most importantly, the compound does not cause memory problems or sedation, which is a common side effect of gabapentin and a common side effect of similar drugs targeting chronic pain.

How it works: Targets the source of pain

SBI-810 performs multiple mechanisms through multiple mechanisms of the peripheral nervous system (nerves of the entire body) and the central nervous system (brain and spinal cord). In the spinal cord, the drug reduces the spread of pain signals between neurons, effectively suppressing pain information before it reaches the brain.

In sensory neurons, SBI-810 inhibits the electrical emission of signal pain and reduces the expression of NAV1.7, a key protein involved in the transmission of pain signals. This dual action allows the drug to block pain at multiple points in the nervous system.

Crucially, SBI-810 makes them more effective at lower doses when tested with opioids, which can reduce opioid use while maintaining pain control. It also prevents common opioid side effects, such as reduced symptoms of constipation and withdrawal, which leads to addiction.

From the laboratory to the patient

Although still in its early stages of development, Duke University researchers aim to start human trials as soon as possible. The university has obtained multiple patents in the discovery, demonstrating its confidence in its potential as a marketable treatment.

The team conceived SBI-810 as a treatment option for a variety of pain scenarios, from post-operative recovery to chronic diseases such as diabetic nerve pain and lower back pain.

The findings of the study are consistent with broader efforts to address the dual crises of pain management and opioid addiction in the United States. Although deaths from drug overdose have begun to decline, a large number of Americans with chronic pain (and limited effective treatments) have encountered urgent public health challenges.

If human trials confirm promising results in animal studies, SBI-810 may represent a major breakthrough in painkillers: a treatment that is sufficient to relieve severe pain but is precise enough to avoid devastating side effects, which makes opioids so problematic.

For millions of Americans between untreated pain and the risk of current medications, this new approach gives a glimpse into the future appearance of pain management – ​​effective relief without high, addiction or reduced returns that have defined pain treatment for generations.