Scientists from the John Innes Centre and Johns Hopkins University have discovered that in some individuals, the cause of hyperhidrosis (excessive sweating without an apparent reason) may lie in a persistently activated nervous “thermostat”—a dysfunction of the sympathetic nervous system. The study was published in the journal Science Advances.
The researchers conducted whole-genome sequencing on 32 families with a hereditary form of hyperhidrosis and identified mutations in the SCN10A gene, which encodes the sodium channel NaV1.8. This protein, previously studied in the context of pain signaling, was found to be expressed also in sympathetic ganglia—nerve clusters that regulate sweating.
In a mouse model carrying the NaV1.8p.R14L mutation, the scientists observed heightened activity of sympathetic neurons in response to cholinergic stimulation. This led to excessive sweating comparable to the clinical presentation in patients. Meanwhile, drugs that block NaV1.8 (A-887826) suppressed sweating by an average of 70%, and in knockout mice (lacking NaV1.8), it decreased by 34%.
The researchers also confirmed that the reverse mutation—NaV1.8p.C1288W, which results in a loss of channel function—reduced sweating in both mice and humans. However, in one patient, this effect was offset by a mutation in the aquaporin AQP5, suggesting a potential interplay between neuronal and glandular mechanisms.
In the clinical portion of the work, the authors demonstrated that anti-hyperhidrosis medications (glycopyrrolate, oxybutynin), as well as guanfacine, effectively reduced sweating in mice with the NaV1.8 mutation. Notably, cannabidiol showed the greatest effect, achieving up to 53% suppression.
The researchers conclude that some cases of hyperhidrosis should be viewed not as a dermatological condition, but as a neurological disorder caused by genetic hyperexcitability of sympathetic neurons. This opens up prospects for targeted therapy and a revision of the disease’s classification.
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