Voltage-gated sodium channels in pain states: Role in pathophysiology and targets for treatment

Sulayman D. Dib-Hajj, Alexander M. Binshtok, Theodore Cummins, Michael F. Jarvis, Tarek Samad, Katharina Zimmermann

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Pain is a major unmet medical need which has been causally linked to changes in sodium channel expression, modulation, or mutations that alter channel gating properties or current density in nociceptor neurons. Voltage-gated sodium channels activate (open) then rapidly inactivate in response to a depolarization of the plasma membrane of excitable cells allowing the transient flow of sodium ions thus generating an inward current which underlies the generation and conduction of action potentials (AP) in these cells. Activation and inactivation, as well as other gating properties, of sodium channel isoforms have different kinetics and voltage-dependent properties, so that the ensemble of channels that are present determine the electrogenic properties of specific neurons. Biophysical and pharmacological studies have identified the peripheral-specific sodium channels Nav1.7, Nav1.8 and Nav1.9 as particularly important in the pathophysiology of different pain syndromes, and isoform-specific blockers of these channels or targeting their modulators hold the promise of a future effective therapy for treatment of pain.

Original languageEnglish
Pages (from-to)65-83
Number of pages19
JournalBrain Research Reviews
Volume60
Issue number1
DOIs
StatePublished - Apr 2009

Fingerprint

Voltage-Gated Sodium Channels
Sodium Channels
Pain
Protein Isoforms
Neurons
Nociceptors
Action Potentials
Therapeutics
Sodium
Cell Membrane
Pharmacology
Ions
Mutation

Keywords

  • Cold nocicptors
  • Cytokines
  • Dorsal root ganglion
  • Genetic of pain
  • Local anesthetics
  • Neurotoxins
  • Pharmacotherapy
  • Sensory neurons
  • Sodium channelopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Voltage-gated sodium channels in pain states : Role in pathophysiology and targets for treatment. / Dib-Hajj, Sulayman D.; Binshtok, Alexander M.; Cummins, Theodore; Jarvis, Michael F.; Samad, Tarek; Zimmermann, Katharina.

In: Brain Research Reviews, Vol. 60, No. 1, 04.2009, p. 65-83.

Research output: Contribution to journalArticle

Dib-Hajj, Sulayman D. ; Binshtok, Alexander M. ; Cummins, Theodore ; Jarvis, Michael F. ; Samad, Tarek ; Zimmermann, Katharina. / Voltage-gated sodium channels in pain states : Role in pathophysiology and targets for treatment. In: Brain Research Reviews. 2009 ; Vol. 60, No. 1. pp. 65-83.
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