A hidden switch in pain and itch disorders microbiologystudy

Nav1.9: the hidden switch in pain and itch
Overview of targeted regions within the C-tail of hNaV1.5 and hNaV1.9. Credit: Science Advances (2025). DOI: 10.1126/sciadv.adt9799

Imagine not feeling any pain when you stub your toe—or, conversely, experiencing constant burning pain or itching without an obvious cause. For some people, this is reality, caused by mutations in a single protein: the sodium channel NaV1.9.

NaV1.9 is a voltage-gated ion channel found in sensory nerve cells that regulates sensitivity to pain and itch—like a “volume knob” for sensation. Yet for years, the channel remained a mystery because it was extremely difficult to study in the lab.

A new study, published in Science Advances and led by Professor Frank Bosmans (Experimental Pharmacology Research Group, VUB), breaks this scientific enigma. His team succeeded, for the first time, in reliably expressing NaV1.9 in a controlled system. This now makes it possible to precisely measure how the channel works and how mutations can cause rare—and sometimes extreme—disorders.

“For fifteen years, no one was able to reliably express NaV1.9,” says Bosmans. “We’ve now developed a method that makes it possible.”

Mutations in the SCN11A gene, which encodes NaV1.9, can lead to total loss of pain sensation, chronic pain or itch, or disorders affecting gut function and sweating. This new method opens up possibilities for diagnosing patients with unexplained pain symptoms and paves the way for targeted therapies—without the downsides of opioids.

“We can now functionally test the impact of specific mutations,” Bosmans explains. “That’s an important step toward personalized medicine.”

Pharmaceutical companies have long shown interest in the system, but until now lacked a reliable platform for testing. NaV1.9 is now seen as a promising target for a new generation of non-addictive painkillers.

More information:
Margaux Theys et al, A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaV 1.9 channels, Science Advances (2025). DOI: 10.1126/sciadv.adt9799

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Unlocking the Naᵥ1.9 channel: A hidden switch in pain and itch disorders (2025, June 3)
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