title: SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model.
abstract: 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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: T R
authors.initials: TR
authors.lastname: Cummins
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.forename: S D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.forename: J A
authors.initials: JA
authors.lastname: Black
authors.forename: S G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: 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*
chemical_list: D015222:Sodium Channels; D002351:Carrageenan