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1 Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
2 Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada
* To whom correspondence should be addressed. E-mail: vanners{at}hdh.kari.net.
The composition of Na+ currents in dorsal root ganglia (DRG) neurons depends upon their neuronal phenotype and innervation target. Two TTX-resistant (TTX-R) Na+ currents have been described in small DRG neurons; one with slow inactivation kinetics (Nav 1.8) and the other with persistent kinetics (Nav 1.9) and their modulation has been implicated in inflammatory pain. This has not been studied in neurons projecting to the colon. This study examined the relative importance of these currents in inflammation - induced changes a mouse model of inflammatory bowel disease. Colonic sensory neurons were retrogradely labeled and colitis induced by instillation of TNBS into the lumen of the distal colon. Seven to ten days later, immunohistochemical properties were characterized in controls and whole cell recordings obtained from small (<40 pF) labeled DRG neurons from control and TNBS animals. Most neurons exhibited both fast TTX- sensitive and slow TTX- R inactivating Na+ currents but persistent TTX-R currents were uncommon (<15%). Most labeled neurons were CGRP (79%), trkA (84%) immunoreactive but only a small minority bind IB4 (14%). TNBS-colitis caused ulceration, thickening of the colon and significantly increased neuronal excitability. The slow TTX- resistant inactivating sodium current density (Nav 1.8) was significantly increased but other sodium currents were unaffected. Most small mouse colonic sensory neurons are CGRP, trkA immunoreactive, but not IB4 reactive and exhibit fast TTX-sensitive, slow TTX-R but not persistent TTX-R Na+ currents. Colitis - induced hyperexcitability is associated with increased slow TTX-R (Nav 1.8) Na+ current. Together, these findings suggest that colitis alters trkA positive neurons to preferentially increase slow TTX-R Na+ (Nav 1.8) currents.
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