Pain relief without addiction? Meet Suzetrigine (JOURNAVX), the next-gen painkiller

New hope for pain relief without addiction risk
Pain management has long relied on medications that affect the brain's pain centers, but many of these come with risks of side effects and addiction.

Among the most concerning are opioids, which can be effective but carry a high potential for dependence.

Researchers have now focused on a different kind of treatment that targets only pain-sensing neurons in the body, not the brain. And it turns out - they have succeeded.

One of the most promising targets is the sodium channel NaV1.8, which plays a crucial role in sending pain signals through the peripheral nerves. This channel is not found in the brain or spinal cord, making it a safer focus for pain relief.

Suzetrigine (it´s also called VX-548 - and no, it is not the name of an Elon Musk kid) is a new drug that selectively blocks NaV1.8.

Unlike other drugs that block many types of sodium channels and cause widespread side effects, suzetrigine acts only on NaV1.8, making it both precise in targeting pain and potentially much safer.

By targeting only this pain-related sodium channel, the drug helps reduce pain without affecting heart, brain, or muscle function.

The goal of this new study was to understand how suzetrigine works and to test whether it could offer effective pain relief without the dangers of addiction.

How Suzetrigine works
Suzetrigine works by binding to a specific part of the NaV1.8 channel. This action keeps the channel in a "closed" state, which stops it from sending pain signals.

This is different from how local anesthetics work on the peripheral nerves. Anesthetics block sodium channels when they are in an "open" state and affect many different types of nerves.

Because suzetrigine only affects NaV1.8 and keeps it closed before it even sends a signal, it offers a unique method of pain control.

In lab tests on human nerve cells from pain-sensing areas, researchers found that suzetrigine could block pain signals at very low doses.

Our nerves transmit signals, including pain signals, via small electrical currents that travel along the nerve. Suzetrigine worked consistently across different types of electrical signals in the nerves and maintained its effect even during repeated firing of the nerves. This means it could help with both sudden and ongoing pain.

No unwanted effects on the brain or heart 
To confirm that suzetrigine only works in the peripheral nervous system and doesn’t affect the brain, researchers examined data from over 1,000 brain and spinal cord samples.

These showed that the NaV1.8 channel simply isn’t present in the brain. That's super important because this makes it very unlikely that a drug targeting NaV1.8 would cause side effects like changes in mood, behavior, or cognition.

Further safety studies were conducted. Even at high doses, there were no signs of changes in behavior, no signs of dependence, and no effects on the cardiovascular system.

Importantly, when taken off the drug suddenly, none experienced withdrawal symptoms - something very common with addictive drugs like opioids.

Strong results in clinical trials
Suzetrigine has already been tested in several phase 3 (last phase before approval) clinical trials involving nearly 2,500 participants with moderate to severe acute pain.

In these trials, the drug showed significant pain relief with very few side effects. It was as effective as commonly used opioid drugs but did not show any signs of causing euphoria or addiction. The most common side effect was mild dizziness, and even this occurred less frequently than in participants given opioids or a placebo.

Patients in open-label studies (where both doctor and patient know which drug is being used) also reported high satisfaction with the treatment. Most rated suzetrigine as good or excellent in controlling their pain.

Because it can be taken by mouth and has a predictable effect, suzetrigine may be especially useful for patients recovering from surgery or experiencing other forms of short-term pain.

Why this could change pain management 
Suzetrigine represents a completely new type of pain medication that works outside the brain, reducing the risk of addiction. Its highly selective action means it avoids the problems caused by less targeted drugs.

It can also be safely combined with other treatments like local anesthetics, without interference or negative interactions. This could allow doctors to tailor pain relief strategies more precisely to each patient.

By blocking pain where it begins—in the nerves—without affecting the brain, suzetrigine may change the way we think about pain relief.

It almost sounds like I’m on Vertex Pharmaceuticals’ payroll—I’m not. Just excited about this new option in pain management, where innovation is very much needed.

About the paper that inspired:

First Author: Jeremiah D. Osteen, USA
Published: Pain and Therapy, April 2025
Link to paper: https://link.springer.com/article/10.1007/s40122-024-00697-0

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