SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model.
It has been suggested that hyperexcitability in dorsal root ganglion (DRG) neurons due to altered sodium channel expression contributes to some chronic pain syndromes. To understand the role of the voltage-gated sodium channel alpha-SNS in inflammatory pain, we investigated the expression of alpha-SNS mRNA and tetrodotoxin-resistant (TTX-R) sodium current in small DRG neurons, which include nociceptive cells, following injection of carrageenan into the hind paw of the rat using in situ hybridization and patch-clamp recording. alpha-SNS mRNA expression in DRG neurons projecting to the inflamed limb was significantly increased 4 days following carrageenan injection, compared with DRG neurons from the contralateral side or naive (uninjected) rats (mean +/- s.d. optical density ratio: ipsilateral/contralateral, 1.77 +/- 0.17; ipsilateral/naive, 1.88 +/- 0.36). The amplitude of the TTX-R sodium current in small DRG neurons projecting to the inflamed limb was significantly larger than on the contralateral side 4 days post-injection (31.7 +/- 3.3 vs 20.0 +/- 2.1 nA). The TTX-R current density was also significantly increased. These results demonstrate the increased expression of alpha-SNS sodium channels in small DRG neurons following injection of carrageenan into their projection field, and suggest that alpha-SNS is involved in the development of hyperexcitability associated with inflammation.
Tanaka
M
M
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cummins
T R
TR
Ishikawa
K
K
Dib-Hajj
S D
SD
Black
J A
JA
Waxman
S G
SG
D000818:Animals; D002351:Carrageenan; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*
D015222:Sodium Channels; D002351:Carrageenan