Tetrodotoxin (TTX) as a therapeutic agent for pain

Mar Drugs. 2012 Feb;10(2):281-305. doi: 10.3390/md10020281. Epub 2012 Jan 31.


Tetrodotoxin (TTX) is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs). VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured) nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.

Keywords: TTX; TTX-sensitive voltage-gated sodium channels; neuropathic pain; pain; tetrodotoxin.

Publication types

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

MeSH terms

  • Acute Pain / drug therapy
  • Acute Pain / immunology
  • Acute Pain / metabolism
  • Analgesics, Non-Narcotic / therapeutic use*
  • Animals
  • Humans
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuralgia / drug therapy
  • Neuralgia / immunology
  • Neuralgia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotoxins / therapeutic use*
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sodium Channel Blockers / therapeutic use*
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Tetrodotoxin / therapeutic use*


  • Analgesics, Non-Narcotic
  • Nerve Tissue Proteins
  • Neurotoxins
  • Protein Isoforms
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin