Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain

Joel A. Black, Shujun Liu, Masaki Tanaka, Theodore R. Cummins, Stephen G. Waxman

Research output: Contribution to journalArticle

317 Scopus citations

Abstract

Nociceptive neurons within dorsal root ganglia (DRG) express multiple voltage-gated sodium channels, of which the tetrodotoxin-resistant (TTX-R) channel Nav1.8 has been suggested to play a major role in inflammatory pain. Previous work has shown that acute administration of inflammatory mediators, including prostaglandin E2 (PGE2), serotonin, and adenosine, modulates TTX-R current in DRG neurons, producing increased current amplitude and a hyperpolarizing shift of its activation curve. In addition, 4 days following injection of carrageenan into the hind paw, an established model of inflammatory pain, Nav1.8 mRNA and slowly-inactivating TTX-R current are increased in DRG neurons projecting to the affected paw. In the present study, the expression of sodium channels Nav1.1-Nav1.9 in small (≤25μmdiameter) DRG neurons was examined with in situ hybridization, immunocytochemistry, Western blot and whole-cell patch-clamp methods following carrageenan injection into the peripheral projection fields of these cells. The results demonstrate that, following carrageenan injection, there is increased expression of TTX-S channels Nav1.3 and Nav1.7 and a parallel increase in TTX-S currents. The previously reported upregulation of Nav1.8 and slowly-inactivating TTX-R current is not accompanied by upregulation of mRNA or protein for Nav1.9, an additional TTX-R channel that is expressed in some DRG neurons. These observations demonstrate that chronic inflammation results in an upregulation in the expression of both TTX-S and TTX-R sodium channels, and suggest that TTX-S sodium channels may also contribute, at least in part, to pain associated with inflammation.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalPain
Volume108
Issue number3
DOIs
StatePublished - Apr 1 2004

Keywords

  • Carrageenan
  • Dorsal root ganglia
  • Inflammatory pain
  • Sodium channel
  • Tetrodotoxin-resistant- sensitive Na current

ASJC Scopus subject areas

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

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