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This Article Full Text Full Text (PDF) All Versions of this Article: 576/1/257    most recent jphysiol.2006.113597v2 jphysiol.2006.113597v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hillsley, K. Articles by Stead, R. H. Search for Related Content PubMed PubMed Citation Articles by Hillsley, K. Articles by Stead, R. H. Related Collections Neuroscience

¹ Holburn Group, Bowmanville, Ontario, Canada
² Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium

Tetrodotoxin-resistant (TTX-R) sodium currents have been proposed to underlie sensory neuronal hyperexcitability in acute inflammatory models, but their role in chronic models is unknown. Since no pharmacological tools to separate TTX-R currents are available, this study employs Na_v1.8 and Na_v1.9 null mice to evaluate these currents roles in a chronic hyperexcitability model after the resolution of an inflammatory insult. Transient jejunitis was induced by infection with Nippostrongylus brasiliensis (Nb) in Na_v1.9 and Na_v1.8 null, wild-type and naïve mice. Retrogradely labelled dorsal root ganglia (DRG) neurons were harvested on day 20–24 post-infection for patch clamp recording. Rheobase and action potential (AP) parameters were recorded as measures of excitability, and Na_v1.9 and Na_v1.8 currents were recorded. DRG neuronal excitability was significantly increased in post-infected mice compared to sham animals, despite the absence of ongoing inflammation (sham = 1.9 ± 0.3, infected = 3.6 ± 0.7 APs at 2x rheobase, P = 0.02). Hyperexcitability was associated with a significantly increased amplitude of TTX-R currents. Hyperexcitability was maintained in Na_v1.9^–/– mice, but hyperexcitability was absent and APs were blunted in Na_v1.8^–/– mice. This study identifies a critical role for Na_v1.8 in chronic post-infectious visceral hyperexcitability, with no contribution from Na_v1.9. Nb infection-induced hyperexcitability is not observed in Na_v1.8^–/– mice, but is still present in Na_v1.9^–/– mice. It is not clear whether hyperexcitability is due to a change in the function of Na_v1.8 channels or a change in the number of Na_v1.8 channels.

(Received 15 May 2006; accepted after revision 17 July 2006; first published online 20 July 2006)
Corresponding author R. H. Stead: Holburn Group, 1100 Bennett Road, Bowmanville, Canada ON L1C 3K5. Email: ronald.stead{at}holburn.com

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