Paroxysmal itch caused by gain-of-function Na(v)1.7 mutation

Grazia Devigili, Roberto Eleopra, Tiziana Pierro, Raffaella Lombardi, Sara Rinaldo, Christian Lettieri, Catharina G. Faber, Ingemar S. J. Merkies, Stephen G. Waxman, Giuseppe Lauria*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

66 Citations (Web of Science)


Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Na(v)1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.
Original languageEnglish
Pages (from-to)1702-1707
Issue number9
Publication statusPublished - Sep 2014


  • Itch
  • Neuropathic pain
  • Sodium channels
  • SCN9A
  • Small nerve fiber
  • Burning pain
  • Paroxysmal

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