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Gain-of-Function Mutation Met136Val in SCN8A is not a Common Cause of Trigeminal Neuralgia
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  • Raymond Sekula,
  • Kathleen Deeley,
  • Hayley Denwood,
  • Alexandre Vieira
Raymond Sekula
University of Pittsburgh
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Kathleen Deeley
University of Pittsburgh
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Hayley Denwood
University of Pittsburgh
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Alexandre Vieira
University of Pittsburgh
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Abstract

Classical trigeminal neuralgia (cTN) is a neuropathic pain disorder marked by evoked and spontaneous attacks in the distribution of the trigeminal nerve, and the disorder is further associated with periods of complete remission and subsequent recurrence in most patients. A mutation in SCN8A, a sodium channel gene that codes for the Nav1.6 protein, was reported in a 64-year-old white female that presented with classical trigeminal neuralgia. The Met136Val change produced a significant increase in peak transient and resurgent currents of Nav1.6, reduced the threshold for action potential in trigeminal ganglia neurons, and enhanced the neuronal evoked response and the fraction of neurons that fire at a higher rate than those expressing wild type channels. We sequenced 123 individuals with a diagnosis of trigeminal neuralgia and did not detect the mutation, suggesting its frequency is lower than 1% in the population.