Voltage-Gated Sodium Channels and Hyperalgesia

Josephine Lai, Frank Porreca, John C. Hunter, Michael S. Gold

Research output: Contribution to journalReview articlepeer-review

265 Scopus citations

Abstract

Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.

Original languageEnglish (US)
Pages (from-to)371-397
Number of pages27
JournalAnnual review of pharmacology and toxicology
Volume44
DOIs
StatePublished - 2004

Keywords

  • Antiarrhythmics
  • Anticonvulsant
  • Inflammation
  • Local anesthetics
  • Neuropathic pain
  • Sensory neuron

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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