Opioids can be highly effective at relieving moderate to severe pain, whether it comes from surgery, an injury or conditions such as cancer. They work by activating opioid receptors in the brain and body, which block pain signals and reduce the feeling of pain. These benefits also come with a serious downside. Opioid misuse and abuse have become a major public health problem worldwide.
Pain requires medication, but vulnerable populations cannot be allowed to fall prey to addiction and overdose. So, a recent clinical trial led by Latigo Biotherapeutics evaluated a new non-opioid pain medication called LTG-001, which works by selectively inhibiting Nav1.8, a voltage-gated sodium channel primarily located in the peripheral nervous system that helps carry pain signals.
The researchers wanted to see how safe this drug is and how well it can reduce moderate-to-severe pain in patients recovering from tummy tuck surgery.
Participants received either a low-dose regimen, a high-dose regimen, a standard opioid painkiller or a placebo. The trial showed positive results for the new non-opioid drug. Both the low and high doses of LTG-001 significantly reduced pain over 48 hours compared with placebo. In fact, the high dose provided greater average pain relief over 48 hours than the opioid painkiller.
The findings are published in the New England Journal of Medicine.Mean NPRS scores over the treatment period (Full Analysis Population). Credit: New England Journal of Medicine (2026). DOI: 10.1056/nejmoa2602910
The Nav1.8 approach
In 2019 alone, nearly 48,000 deaths were linked to opioid use, accounting for around 80% of all drug-related deaths worldwide. Even if someone is not addicted to the drugs, opioids have other drawbacks, including nausea, constipation and vomiting. Despite these risks, doctors prescribe opioids because they are effective pain relievers, and non-opioid alternatives usually are not strong enough to have the same effect.
After years of testing multiple non-opioid alternatives, scientists identified a potential drug target: Nav1.8. This sodium ion channel is found mainly in nociceptors and dorsal root ganglia, which are specialized sensors of the nervous system. Since the channel plays a key role in transmitting pain signals, blocking it offers a promising way to treat acute and chronic pain without the addiction risk associated with opioids.
In 2025, suzetrigine became the first Nav1.8 inhibitor to be approved as a pain medication in this class in decades. However, suzetrigine showed only modest pain relief in trials, and a subsequent, supposedly stronger follow-up drug failed to outperform a placebo.
LTG-001 is an oral drug designed to go beyond the limits of earlier Nav1.8 inhibitors. It is highly potent and can penetrate deep into peripheral nerves, reaching the site where pain signals originate and blocking Nav1.8.
Inside the surgery trial
So far, researchers have mainly evaluated Nav1.8 inhibitors based on how well they block the Nav1.8 channel in laboratory tests. In this study, the researchers went beyond that. With safety and dosing established in Phase I, they moved to a Phase IIb double-blind, randomized, placebo-controlled trial involving 343 adults ages 18–65. All participants were recovering from lower abdominal tummy tuck surgery and had a pain score of at least 5 out of 10 within four hours after surgery.
Researchers randomly divided patients into four equal groups and treated them for 48 hours. Two groups received LTG-001: one at a low dose of 300 mg initially, followed by 150 mg every 12 hours, and the other at a high dose of 450 mg initially, followed by 300 mg every 12 hours. A third group received 5 mg hydrocodone plus 325 mg acetaminophen every six hours, while the fourth received a placebo.
LTG-001 delivered significantly greater pain relief over 48 hours than placebo. The high-dose group had an average pain reduction score of 185.30, compared with 161.05 for the low-dose group. Both doses provided meaningful pain relief within an hour of treatment, which was faster than the standard opioid group (82.8 minutes) and the placebo group (87.5 minutes). Also, more than half of patients on the high dose (52%) completed recovery without needing any backup opioid, compared with just 22% of those who received placebo.
The researchers note that some results with LTG-001 were similar to those seen with hydrocodone-acetaminophen. Still, the two drugs were not directly compared, so it is too early to say whether one is better or equally effective. If larger trials confirm that LTG-001 is both safe and effective, it could give doctors another way to manage postsurgical pain without relying on opioids.