By Ed Sutton, MD
Suzetrigine marketed as JOURNAVX by Vertex Pharmaceuticals is the first new analgesic with a novel mechanism of action to be FDA approved in two decades.
As anesthesia providers we need to have an understanding of this new mechanism of action, as new similar molecules will likely be developed in the future.
Anesthesiology, June 1st, 2025 published two large randomized, double-blind, placebo controlled studies involving abdominoplasty and bunionectomy, suzetrigine was found to be as efficacious as hydrocodone/acetaminophen (Percocet) without the risk of severe side effects, misuse, and potential for addiction. Suzetrigine also has an excellent safety profile compared to other commonly used analgesics, NSAIDs (bleeding and GI side effects), acetaminophen (liver toxicity), and the gabapentinoids (dementia).
Suzetrigine inhibits the voltage-gated sodium channels, NaV1.8, which are highly expressed in peripheral afferent nociceptors (pain fibers). This is a totally new mechanism of action for an analgesic medication. Inhibiting NaV1.8 channels prevents action potentials from being transmitted from the periphery into the spinal cord, providing non-opioid pain relief, as efficacious as hydrocodone. Much is known of NaV1.8 channels as they have been extensively researched for at least 15 years, and now we have an agent that acts very selectively at this site without interfering with other sodium gated channels. The gene location that encodes for NaV1.8 is known to be SCN10A and loss-of-function and gain-of-function mutation studies are underway, trying to find a link with chronic pain conditions, and the potential to find some future pharmacogenetic therapy to solve the problem of chronic pain.
As anesthesia providers, I believe it’s important for us to have an understanding of pain control pharmacology, and manipulation of the NaV1.8 channel (at least for our boards exams) and suzetrigine is an exciting new expansion of pain control science. JOURNAVX is THE first in this new class of analgesic. In an attempt to prevent accidents and confusion the FDA is now tasked to give final consent for all trade names to new drugs. Companies usually give no explanation as to the etymology of their assigned names. Vertex Pharmaceutical gave suzetrigine (VX-548) the trade name JOURNAVX, possibly a new day (Jour) for a novel pain receptor blocker, NaV1.8, by Vertex Pharmaceuticals. Hopefully any new subsequent drug in this category will have NAV in their trade name, making them easier to identify.
