Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Pain. 2014 Sep;155(9):1702-1707. doi: 10.1016/j.pain.2014.05.006. Epub 2014 May 10.

Abstract

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 Nav1.7 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.

Keywords: Burning pain; Itch; Neuropathic pain; Paroxysmal; SCN9A; Small nerve fiber; Sodium channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antipruritics / therapeutic use
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Mutation*
  • NAV1.7 Voltage-Gated Sodium Channel / genetics*
  • Pain / drug therapy
  • Pain / genetics*
  • Pain / physiopathology
  • Pain Threshold / physiology
  • Physical Stimulation
  • Pregabalin
  • Pruritus / drug therapy
  • Pruritus / genetics*
  • Pruritus / physiopathology
  • Treatment Outcome
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Antipruritics
  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Pregabalin
  • gamma-Aminobutyric Acid