Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain

Stephen G. Waxman, Theodore Cummins, Sulayman Dib-Hajj, Jenny Fjell, Joel A. Black

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Following nerve injury, primary sensory neurons (dorsal root ganglion [DRG] neurons, trigeminal neurons) exhibit a variety of electrophysiological abnormalities, including increased baseline sensitivity and/or hyperexcitability, which can lead to abnormal burst activity that underlies pain, but the molecular basis for these changes has not been fully understood. Over the past several years, it has become clear that nearly a dozen distinct sodium channels are encoded by different genes and that at least six of these (including at least three distinct DRG- and trigeminal neuronspecific sodium channels) are expressed in primary sensory neurons. The deployment of different types of sodium channels in different types of DRG neurons endows them with different physiological properties. Dramatic changes in sodium channel expression, including downregulation of the SNS/PN3 and NaN sodium channel genes and upregulation of previously silent type III sodium channel gene, occur in DRG neurons following axonal transection. These changes in sodium channel gene expression are accompanied by a reduction in tetrodotoxin (TTX)-resistant sodium currents and by the emergence of a TTX- sensitive sodium current which recovers from inactivation (reprimes) four times more rapidly than the channels in normal DRG neurons. These changes in sodium channel expression poise DRG neurons to fire spontaneously or at inappropriately high frequencies. Changes in sodium channel gene expression also occur in experimental models of inflammatory pain. These observations indicate that abnormal sodium channel expression can contribute to the molecular pathophysiology of pain. They further suggest that selective blockade of particular subtypes of sodium channels may provide new, pharmacological approaches to treatment of disease involving hyperexcitability of primary sensory neurons.

Original languageEnglish
Pages (from-to)1177-1187
Number of pages11
JournalMuscle and Nerve
Volume22
Issue number9
DOIs
StatePublished - Sep 1999
Externally publishedYes

Fingerprint

Sodium Channels
Sensory Receptor Cells
Spinal Ganglia
Pain
Neurons
Tetrodotoxin
NAV1.8 Voltage-Gated Sodium Channel
Sodium
Genes
Gene Expression
Theoretical Models
Up-Regulation
Down-Regulation
Pharmacology

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain. / Waxman, Stephen G.; Cummins, Theodore; Dib-Hajj, Sulayman; Fjell, Jenny; Black, Joel A.

In: Muscle and Nerve, Vol. 22, No. 9, 09.1999, p. 1177-1187.

Research output: Contribution to journalArticle

Waxman, Stephen G. ; Cummins, Theodore ; Dib-Hajj, Sulayman ; Fjell, Jenny ; Black, Joel A. / Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain. In: Muscle and Nerve. 1999 ; Vol. 22, No. 9. pp. 1177-1187.
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