Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain.
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.
Black
Joel A
JA
Department of Neurology and Paralyzed Veterans of America, Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven, CT 06510, USA Rehabilitation Research Center, VA Connecticut Healthcare System, 950 Campbell Ave, West Haven, CT, 06516 USA Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Liu
Shujun
S
Tanaka
Masaki
M
Cummins
Theodore R
TR
Waxman
Stephen G
SG
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002351:Carrageenan; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D012333:RNA, Messenger; D015222:Sodium Channels; C023790:tetrodotoxin-binding protein; D013779:Tetrodotoxin; D002351:Carrageenan