Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics

Annu Rev Neurosci. 2019 Jul 8:42:87-106. doi: 10.1146/annurev-neuro-070918-050144. Epub 2019 Jan 31.


Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the need for better therapies. Molecular genetic studies have now linked multiple human pain disorders to voltage-gated sodium channels, including disorders characterized by insensitivity or reduced sensitivity to pain and others characterized by exaggerated pain in response to normally innocuous stimuli. Here, we review recent developments that have enhanced our understanding of pathophysiological mechanisms in human pain and advances in targeting sodium channels in peripheral neurons for the treatment of pain using novel and existing sodium channel blockers.

Keywords: congenital insensitivity to pain; erythromelalgia; induced pluripotent cells; ion channels; nociceptors; painful peripheral neuropathy; paroxysmal extreme pain disorder; pharmacogenomics; tetrodotoxin-resistant; tetrodotoxin-sensitive.

Publication types

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

MeSH terms

  • Animals
  • Carbamazepine / pharmacology
  • Carbamazepine / therapeutic use
  • Drug Evaluation, Preclinical
  • Forecasting
  • Ganglia, Spinal / physiopathology
  • Genetic Association Studies
  • Humans
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Peripheral Nerves / physiopathology
  • Pharmacogenomic Testing
  • Protein Domains
  • Sensory Receptor Cells / physiology
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use*
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / physiology*
  • Somatoform Disorders / drug therapy
  • Somatoform Disorders / genetics
  • Somatoform Disorders / physiopathology*
  • Structure-Activity Relationship


  • Nerve Tissue Proteins
  • Sodium Channel Blockers
  • Sodium Channels
  • Carbamazepine