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

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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

122 Scopus citations

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 languageAmerican English
Pages (from-to)65-83
Number of pages19
JournalBrain Research Reviews
Volume60
Issue number1
DOIs
StatePublished - Apr 2009
Externally publishedYes

Bibliographical note

Funding Information:
SDH was supported in part by grants from the Rehabilitation Research Service and Medical Research Service, Department of Veterans Affairs, and the Erythromelalgia Association. TRC was supported by a grant from the National Institutes of Health NINDS (NS054642).

Keywords

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

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