Voltage-gated sodium channels and the molecular pathogenesis of pain: A review

Stephen G. Waxman, Theodore R. Cummins, Sulayman D. Dib-Hajj, Joel A. Black

Research output: Contribution to journalReview article

88 Scopus citations

Abstract

Pain pathways begin with spinal sensory (dorsal root ganglion, DRG) neurons that produce nociceptive signals and convey them centrally. Following injury to the nervous system, DRG neurons can become hyperexcitable, generating spontaneous action potentials or abnormal high-frequency activity that contributes to chronic pain. Because the generation of action potentials in DRG neurons depends on voltage-gated sodium channels, an understanding of the expression and function of these channels in DRG neurons is important for an understanding of pain. Molecular studies have indicated that at least eight distinct voltage-gated sodium channels, sharing a common overall motif but encoded by different genes that endow them with different amino acid sequences, are present within the nervous system. The DRG neurons express six different sodium channels, including several sensory-neuron-specific sodium channels that are not present at significant levels within other parts of the nervous system. Following injury to their axons within peripheral nerve, DRG neurons down-regulate some sodium channel genes, and up-regulate others. As a result, a different repertoire of sodium channels is inserted into the DRG neuron cell membrane following injury, which is a molecular change that is accompanied by changes in physiological properties that contribute to hyperexcitability in these cells. Sodium channel expression is also altered in experimental models of inflammatory pain. The multiplicity of sodium channels, and the dynamic nature of their expression, makes them important targets for pharmacologic manipulation in the search for new therapies for pain.

Original languageEnglish (US)
Pages (from-to)517-528
Number of pages12
JournalJournal of Rehabilitation Research and Development
Volume37
Issue number5
StatePublished - Dec 1 2000
Externally publishedYes

Keywords

  • DRG neuron
  • Hyperexcitability
  • Ion channels
  • Nerve injury
  • Neuropathic pain

ASJC Scopus subject areas

  • Rehabilitation

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