The roles of sodium channels in nociception: Implications for mechanisms of pain

Theodore Cummins, Patrick Sheets, Stephen G. Waxman

Research output: Contribution to journalArticle

323 Citations (Scopus)

Abstract

Understanding the role of voltage-gated sodium channels in nociception may provide important insights into pain mechanisms. Voltage-gated sodium channels are critically important for electrogenesis and nerve impulse conduction, and a target for important clinically relevant analgesics such as lidocaine. Furthermore, within the last decade studies have shown that certain sodium channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and that the expression and functional properties of voltage-gated sodium channels in peripheral sensory neurons can be dynamically regulated following axonal injury or peripheral inflammation. These data suggest that specific voltage-gated sodium channels may play crucial roles in nociception. Experiments with transgenic mice lines have clearly implicated Nav1.7, Nav1.8 and Nav1.9 in inflammatory, and possibly neuropathic, pain. However the most convincing and perhaps most exciting results regarding the role of voltage-gated sodium channels have come out recently from studies on human inherited disorders of nociception. Point mutations in Nav1.7 have been identified in patients with two distinct autosomal dominant severe chronic pain syndromes. Electrophysiological experiments indicate that these pain-associated mutations cause small yet significant changes in the gating properties of voltage-gated sodium channels that are likely to contribute substantially to the development of chronic pain. Equally exciting, recent studies indicate that recessive mutations in Nav1.7 that eliminate functional current can result in an apparent complete, and possibly specific, indifference to pain in humans, suggesting that isoform specific blockers could be very effective in treating pain. In this review we will examine what is known about the roles of voltage-gated sodium channels in nociception.

Original languageEnglish
Pages (from-to)243-257
Number of pages15
JournalPain
Volume131
Issue number3
DOIs
StatePublished - Oct 2007

Fingerprint

Voltage-Gated Sodium Channels
Nociception
Sodium Channels
Pain
Sensory Receptor Cells
Chronic Pain
Protein Isoforms
Mutation
Neural Conduction
Neuralgia
Lidocaine
Point Mutation
Transgenic Mice
Action Potentials
Analgesics
Inflammation
Wounds and Injuries

Keywords

  • Inherited pain
  • Nociceptive neuron
  • Sodium channel
  • Sodium current

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

The roles of sodium channels in nociception : Implications for mechanisms of pain. / Cummins, Theodore; Sheets, Patrick; Waxman, Stephen G.

In: Pain, Vol. 131, No. 3, 10.2007, p. 243-257.

Research output: Contribution to journalArticle

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