Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8

Josephine Lai, Michael S. Gold, Chang Sook Kim, Di Biana, Michael H. Ossipov, John C. Hunterc, Frank Porreca

Research output: Contribution to journalArticle

370 Scopus citations

Abstract

Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of sodium channels at the site of injury. Here, we show that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral tetrodotoxin (TTX)-resistant sodium channel, NaV1.8, resulted in a time-dependent uptake of the ODN by dorsal root ganglion (DRG) neurons, a selective 'knock-down' of the expression of NaV1.8, and a reduction in the slow-inactivating, TTX-resistant sodium current in the DRG cells. The ODN treatment also reversed neuropathic pain induced by spinal nerve injury, without affecting non-noxious sensation or response to acute pain. These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain.

Original languageEnglish (US)
Pages (from-to)143-152
Number of pages10
JournalPain
Volume95
Issue number1-2
DOIs
StatePublished - Jan 29 2002

Keywords

  • Antisense
  • Dorsal root ganglia
  • Neuropathic pain
  • Peripheral neuron type 3 sodium channel (PN3)
  • Sensory neuron-specific sodium channel (SNS)
  • Sensory neurons
  • Tetrodotoxin-resistant sodium current
  • Voltage sensing sodium channel type 1.8 (NaV1.8)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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