Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use

Lancet Neurol. 2014 Nov;13(11):1152-1160. doi: 10.1016/S1474-4422(14)70150-4.

Abstract

Human studies have firmly implicated voltage-gated sodium channels in human pain disorders, and targeted and massively parallel genomic sequencing is beginning to be used in clinical practice to determine which sodium channel variants are involved. Missense substitutions of SCN9A, the gene encoding sodium channel NaV1.7, SCN10A, the gene encoding sodium channel NaV1.8, and SCN11A, the gene encoding sodium channel NaV1.9, produce gain-of-function changes that contribute to pain in many human painful disorders. Genomic sequencing might help to establish a diagnosis, and in the future might support individualisation of therapeutic approaches. However, in many cases, and especially in sodium channelopathies, the results from genomic sequencing can only be appropriately interpreted in the context of an extensive functional assessment, or family segregation analysis of phenotype and genotype.

Publication types

  • Review

MeSH terms

  • Animals
  • Genotype*
  • Humans
  • Mutation, Missense / genetics
  • Pain / diagnosis*
  • Pain / genetics*
  • Phenotype*
  • Practice Guidelines as Topic
  • Sodium Channels / genetics*

Substances

  • Sodium Channels