Burned soles, bright idea

Picture this: In a bustling street in northern Pakistan, a young boy calmly walks barefoot across burning coals. No flinching. No wincing. No pain. He’s not performing a stunt or enduring some rite of passage - he simply doesn’t feel it.

If I’d seen it firsthand, my wife probably would’ve joked that I can’t even fold a fitted sheet without injury… and that would’ve been the end of it.

But for one geneticist, this moment launched a scientific breakthrough in the making: how to shut off pain without triggering the dangerous side effects of traditional drugs.

It’s in the genes

The implications were massive. If a single gene could switch off pain without dulling the rest of the nervous system, maybe a drug could do the same thing. That insight lit a fire under the bare feet of the pharmaceutical world.

Since then, researchers and biotech startups have been chasing ways to replicate the “firewalker effect,” especially on Nav1.7 and its close cousin Nav1.8, which emerged as a particularly promising target for safe, non-addictive pain relief.

Cutting off pain at the source, not the brain

Let’s say you have a bed of fire in your hallway (or your kid leaves a Lego minefield next to a skateboard... and a banana peel). You step. That white-hot “ouch” signal? It’s powered by a tiny voltage-gated sodium channel in your peripheral nerves called Nav1.8.

What makes Nav1.8 special is that it lives mostly in nociceptors, the nerve fibers specifically designed to detect and transmit pain. It’s basically the switchboard operator for "Damn this hurts!" What makes it compelling as a drug target is that it’s not found in the parts of your nervous system that control things like mood, memory, or movement. It’s pain-specific, which means blocking it can shut down pain without knocking out everything else.

Suzetrigine: a next-gen painkiller that skips the brain entirely

Suzetrigine is a highly selective Nav1.8 inhibitor - an oral drug that intercepts pain signals before they reach the brain. No euphoria, no sedation, no addiction. Just a clean, targeted block of the source of pain.

Companies like Vertex have been working on sodium channel modulators for years, refining molecules to be ultra-selective. Suzetrigine is at least 30,000 times more selective for Nav1.8 than for other sodium channels.

Is it better than opioids for pain management?

We’re not doctors, so don’t take our advice. But… yes? Or at least, Nav1.8 inhibitors like suzetrigine represent a fundamentally new approach to pain relief:

• Targeted Action in the Peripheral Nervous System: Nav1.8 is found mostly in pain-sensing nerves. Blocking it stops pain before it reaches the brain or spinal cord.

• No Addiction Risk: Unlike opioids, Nav1.8 inhibitors don’t affect the brain’s reward system. No euphoria, no risk of abuse.

• Fewer Side Effects: Highly selective action avoids common opioid issues like sedation, confusion, and constipation, while preserving mental clarity.

• Promise for Chronic and Hard-to-Treat Pain: Nav1.8 inhibitors have shown promise in preclinical and clinical studies for reducing pain in difficult cases, potentially offering relief where other drugs fall short.

• Minimal Tolerance Buildup: They don’t rely on brain pathways, making them less likely to require escalating doses over time.

Let’s go! Bring it home Vertex!

Founded in 1989, Vertex Pharmaceuticals is a Boston-based biotechnology company with a strong track record of developing first-in-class, small-molecule drugs, most notably for cystic fibrosis. Vertex spent more than a decade developing suzetrigine (formerly VX-548), investing significant resources in both research and clinical trials.

Regulatory green lights and what’s next

Now branded JOURNAVX, suzetrigine just made history as the first FDA-approved oral Nav1.8 inhibitor. And the first new class of pain drug approved in over 20 years. Read that again. Over two decades since the FDA approved a different pain drug class.

The January 2025 approval covers moderate to severe acute pain in adults, and it came with FDA Fast Track and Breakthrough Therapy designations, which are reserved for treatments that could truly be game changers.

• Commercial Launch: With FDA approval secured, Vertex is rolling out JOURNAVX for acute pain in the U.S. market.

• Expanded Indications: Vertex is pushing forward with late-stage trials for chronic and neuropathic pain, aiming to broaden suzetrigine’s label to include conditions like diabetic peripheral neuropathy and lumbosacral radiculopathy.

• Long-Term Data: Ongoing studies will further clarify suzetrigine’s long-term safety, efficacy, and potential role in reducing opioid reliance. As well as rollout to other countries.

⚡Why we said Hell Yeah!

This is a massive swing at one of medicine’s biggest problems.

Every year, 80+ million Americans are prescribed meds for acute pain, and millions more live with chronic pain that erodes their quality of life, productivity, and mental health. The default solution? Opioids. Effective? Kind of. But they come with addiction, overdose, and economic devastation.

It’s hard to find a single group of clinicians or politicians who would disagree we need to move on from opioids and need better pain tools.

Nav1.8 inhibitors like suzetrigine represent a radical shift. They don’t dull your entire nervous system or hijack your brain’s reward circuitry. Instead, they cut pain off at the periphery nerves without the sedation, confusion, or addiction risk. And that’s not just an upgrade; it’s a new class of medicine. The first new painkiller modality approved in over two decades.

And yeah, the science is wild. But the origin story? Straight-up superhero stuff.

The whole field traces back to a kid in Pakistan who could walk across burning coals without flinching. That single mutation, in a gene regulating sodium channels, cracked open an entirely new understanding of pain. Straight-up X-Men.

It’s a reminder that the next great leap in medicine doesn’t always come from a lab, it can start with a barefoot child walking across fire.

This is innovation with heart, precision, and massive potential scale. That’s why we said hell yeah!

Dive in Deeper

FDA announcement of approval of suzetrigine

Scientific American article detailing the journey from firewalker to suzetrigine

Sanjay Gupta (CNN): “New pain medication originated from fire walkers' gene”

The Neurological Side of Firewalking “There’s no logical explanation.” -Ron Sato, MD, Stanford Medical School, Burns & Plastic Surgery

Official JOURNAVX website

Engage with Nav1.8/Vertex ⚡

In this case we’d really prefer it if you didn’t engage further. 🤔😬

…other than maybe by buying some swag. We’ll donate 50% of profits to a Opioid addiction cause (TBD). We’re gathering “pre-orders” for these sweatshirts, which we expect will cost ~$[60]. Email us at [email protected] if you’re interested.

Nav1.8 + Hell Yeah ⚡