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

Pain. 2004 Apr;108(3):237-247. doi: 10.1016/j.pain.2003.12.035.


Nociceptive neurons within dorsal root ganglia (DRG) express multiple voltage-gated sodium channels, of which the tetrodotoxin-resistant (TTX-R) channel Na(v)1.8 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, Na(v)1.8 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 Na(v)1.1-Na(v)1.9 in small (< or = 25 micromdiameter) 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 Na(v)1.3 and Na(v)1.7 and a parallel increase in TTX-S currents. The previously reported upregulation of Na(v)1.8 and slowly-inactivating TTX-R current is not accompanied by upregulation of mRNA or protein for Na(v)1.9, 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Blotting, Western / methods
  • Carrageenan
  • Cells, Cultured
  • Disease Models, Animal
  • Functional Laterality / drug effects
  • Ganglia, Spinal / pathology*
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Inflammation / chemically induced
  • Inflammation / complications
  • Male
  • Membrane Potentials / drug effects
  • Neurons / metabolism*
  • Pain / chemically induced
  • Pain / metabolism*
  • Patch-Clamp Techniques / methods
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology


  • Anesthetics, Local
  • RNA, Messenger
  • Sodium Channels
  • tetrodotoxin-binding protein
  • Tetrodotoxin
  • Carrageenan