Journavx for Endometriosis Pain: Why We Were Among the First — and Why Sodium Channels Belong at the Center of Endo Care

By Andrea Vidali, MD — Founder, ESSI

Endometriosis is a nerve disease as much as it is a lesion disease.

That sentence is the single most important reframe of the last decade in our field, and it is the lens through which our team at ESSI has approached pain — surgical, post-operative, and chronic — for years.

When the FDA approved Journavx (suzetrigine) in January 2025 as the first-in-class oral selective NaV1.8 sodium-channel blocker, we did not wait. Within weeks of approval, we began integrating it into our post-operative care pathways. Today, nearly a year later, every endometriosis excision patient at ESSI is offered Journavx as part of their recovery protocol, and we believe we are among the first practices in the country to have built it formally into endometriosis care.

This commentary explains why.

The nerve problem nobody wanted to name

For most of its modern history, endometriosis was framed as a problem of misplaced tissue. Pain, in that model, was a downstream symptom — something that followed the lesion. If you removed the lesion, the pain would resolve. When it didn’t, the patient was often told the disease was “back,” or worse, that the pain was psychological.

That model is incomplete, and the cost of its incompleteness has been borne almost entirely by patients.

We now understand that endometriosis remodels the peripheral nervous system. Lesions sprout new nerve fibers (neuroangiogenesis), recruit mast cells and macrophages, release pro-nociceptive cytokines and neurotrophins, and progressively sensitize the sensory neurons that innervate the pelvis. Over time, the peripheral signal becomes loud enough to drive central sensitization in the spinal cord and brain.

This is why some patients with minimal visible disease have severe pain, and why some patients still hurt after complete excision: the surgery removes the lesion, but the nerve has already been rewired.

At ESSI, this is not a peripheral observation. It is the foundation of how we operate, how we counsel patients, and how we manage pain before, during, and after surgery. It is why we perform nerve-aware excision, why we use targeted neuromodulation with botulinum toxin in select anatomical territories, and why we have always paid close attention to the molecular biology of the pain signal itself.

If endometriosis is a nerve disease, then a drug that selectively silences the pain nerve — without touching the brain — is not a side note. It is exactly the kind of tool the field has been waiting for.

What sodium channels are, and why they matter

Every pain signal you have ever felt began as an electrical event. When a sensory nerve in the pelvis is irritated — by inflammation, by a lesion pressing on tissue, by surgical trauma — voltage-gated sodium channels embedded in the nerve membrane open. Sodium ions flood in. The membrane depolarizes. An action potential fires, travels up the nerve, crosses into the spinal cord, and ultimately reaches the brain, where it is interpreted as pain.

Sodium channels are, in a real sense, the on-switch for pain.

There are nine of them in the human body, named NaV1.1 through NaV1.9. Most of them do other things — NaV1.1, 1.2, 1.3, and 1.6 are central nervous system channels; NaV1.4 governs skeletal muscle; NaV1.5 runs the cardiac action potential. Touching those is dangerous, which is why lidocaine, a non-selective sodium-channel blocker, can be lifesaving as a local anesthetic but lethal if it reaches the bloodstream in any quantity.

But three of the nine channels live almost exclusively on peripheral pain-sensing neurons:

• NaV1.7 (gene: SCN9A) — the “threshold” channel. People born without functional NaV1.7 are congenitally insensitive to pain. People with gain-of-function mutations have devastating pain syndromes like erythromelalgia. NaV1.7 has been the holy grail of non-opioid analgesia for two decades, and there is recent and compelling work — including from groups studying endometriosis specifically — implicating NaV1.7 in endometriosis-associated chronic pelvic pain.

• NaV1.8 (gene: SCN10A) — the inflammatory and neuropathic pain workhorse. NaV1.8 is the dominant channel driving the sustained firing of sensitized pain neurons. It is not expressed in the central nervous system, which makes it an exceptionally clean target: block it, and you silence peripheral pain without sedation, euphoria, respiratory depression, or addiction risk. This is the channel Journavx blocks.

• NaV1.9 (gene: SCN11A) — involved in cold pain sensing, small-fiber neuropathy, and persistent inflammatory pain. NaV1.9 is harder to drug but is an active area of development.

Pharmacology has been chasing this family for years. NaV1.7 selective inhibitors have stumbled repeatedly in clinical trials, largely because of how hard it is to achieve enough channel occupancy at safe doses. NaV1.9 drugs are still upstream. NaV1.8 was the channel that finally crossed the finish line — and Journavx (suzetrigine), developed by Vertex Pharmaceuticals, was the first to do it.

How Journavx works

Suzetrigine is a small molecule that selectively binds and inhibits NaV1.8. Functionally, it acts like a targeted, oral version of a local anesthetic — except that, instead of numbing tissue at the injection site, it travels through the bloodstream and selectively silences NaV1.8 wherever sensitized peripheral pain neurons are firing.

Because NaV1.8 is not present in the brain, spinal cord, heart, or skeletal muscle, the drug delivers analgesia without the systemic toll of opioids or the cognitive fog of gabapentinoids.

In the pivotal trials that supported FDA approval, suzetrigine produced a statistically significant reduction in moderate-to-severe acute post-surgical pain compared to placebo over 48 hours. Importantly, the comparator arm included hydrocodone/acetaminophen — a standard opioid combination. Journavx held its own. For the first time in more than two decades, the FDA approved a genuinely new mechanism of action for acute pain.

The side-effect profile is mild: most commonly itching, muscle spasm, and transient elevations in creatine kinase. There is no addiction signal. There is no respiratory depression. Patients can drive, work, parent, and sleep without the dissociation and constipation that have made the opioid recovery experience traumatic for so many of our patients.

Why ESSI moved first

Adopting a new molecule within weeks of approval is not something we do casually. We are conservative about pharmacology and aggressive about science. The reason we moved on Journavx is that the mechanism mapped perfectly onto a problem we already understood:

• Endometriosis pain is driven, in significant part, by sensitized peripheral nociceptors.

• Those nociceptors fire through NaV1.7, NaV1.8, and NaV1.9.

• Surgical excision creates a window of acute post-operative pain layered on top of a chronically sensitized nervous system — exactly the worst-case scenario for opioid escalation, persistent post-surgical pain, and chronic pain transition.

A selective, non-opioid, peripherally restricted NaV1.8 blocker addresses that window with a mechanism that is biologically aligned with the disease.

Within weeks of FDA approval, we incorporated Journavx into our standard post-operative pathway for laparoscopic excision. Nearly a year later, we have used it across hundreds of complex excision cases — bowel, bladder, ureterolysis, diaphragmatic, deep infiltrating disease.

The pattern that has emerged in our practice is consistent: lower opioid requirements, more lucid recoveries, better sleep in the first 72 hours, and patients who describe their post-op experience in language we frankly had not heard before. Patients tell us, repeatedly, that their recovery from a complex multi-organ excision was easier than recoveries they had previously had from much smaller surgeries.

That is the mechanism speaking.

The case for expanding use beyond the post-op window

Journavx is currently approved for moderate-to-severe acute pain. That label is appropriate for the data that exists, and we prescribe within it.

But it is worth saying plainly, as a clinician who treats this disease every week: the indication, as written, is narrower than the biology suggests.

Endometriosis flares are acute pain events. A ruptured endometrioma is an acute pain event. A bowel-deviation cramp, a bladder spasm in a patient with deep infiltrating disease, a cyclical sciatic flare from a sacral plexus implant — these are acute pain events occurring on a chronic substrate. The patients experiencing them are routinely under-treated, pushed toward NSAIDs that damage their gut and their kidneys, opioids that they (rightly) do not want, or hormonal suppression that does not address the pain in real time.

A peripherally selective, non-addictive, fast-acting oral analgesic with a clean cognitive profile is exactly what this patient population needs.

The trial work to extend the indication into chronic pelvic pain, into endometriosis-specific flare management, and into adjunctive use alongside hormonal and surgical care needs to happen. We are advocating for it. We believe Vertex and the broader pain-medicine community should hear, clearly, from endometriosis surgeons that this drug has a role beyond the acute post-surgical window.

Equally, we need the next generation of sodium-channel drugs. A truly selective NaV1.7 inhibitor with adequate channel occupancy would be transformative. A NaV1.8/NaV1.9 combination strategy would likely outperform either alone. The early Journavx data validates the entire family as a drug class. That validation should accelerate, not slow, investment in the rest of the family.

What this means for patients

If you are scheduled for endometriosis excision surgery — at ESSI or elsewhere — Journavx should be part of the conversation. Ask your surgeon whether they are using it, how they are using it, and whether their post-operative pathway has been updated to incorporate non-opioid sodium-channel blockade as a first-line option rather than an afterthought.

If you are living with endometriosis and your acute flares are being managed with escalating opioids, or with nothing at all, this is a conversation worth having with your physician. The drug is approved for moderate-to-severe acute pain. Endometriosis flares qualify. The label is on your side.

And if you are a clinician treating this disease, we would say this: the nerve-centric model of endometriosis is no longer fringe. It is where the science is. The sodium-channel family is where the drugs are coming. Journavx is the first; it will not be the last. Building your practice around the biology of peripheral sensitization — surgically, pharmacologically, and procedurally — is no longer optional for anyone who wants to take this disease seriously.

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About the author. Andrea Vidali, MD, is a reproductive immunologist and endometriosis surgeon, founder of Endometriosis Surgical Specialists International (ESSI) and internationalendo.com, and Director of BRI/ESSI Reproductive Immunology. He practices in New York and collaborates with ESSI surgical colleagues nationally on complex excision and nerve-aware endometriosis care.

Disclosures. Dr. Vidali has no financial relationship with Vertex Pharmaceuticals. ESSI does not receive compensation for prescribing Journavx. This commentary reflects clinical experience and editorial judgment, not promotional content.