Voltage-gated sodium channels and hyperalgesia

Annu Rev Pharmacol Toxicol. 2004;44:371-97. doi: 10.1146/annurev.pharmtox.44.101802.121627.

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.

Publication types

  • Review

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Anesthetics, Local / pharmacology
  • Anesthetics, Local / therapeutic use
  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology*
  • Inflammation / physiopathology
  • Ion Channel Gating*
  • Neurons, Afferent / physiology
  • Pain / physiopathology
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / physiopathology
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Analgesics
  • Anesthetics, Local
  • Anticonvulsants
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin