TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons

This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular rec...

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Bibliographic Details
Published in:	American journal of physiology: Gastrointestinal and liver physiology Vol. 282; no. 6; p. G1045
Main Authors:	Moore, Beverley A, Stewart, Timothy M R, Hill, Ceredwyn, Vanner, Stephen J
Format:	Journal Article
Language:	English
Published:	United States 01-06-2002
Subjects:	4-Aminopyridine - pharmacology Abdominal Pain - chemically induced Abdominal Pain - physiopathology Action Potentials - drug effects Action Potentials - physiology Animals Female Ganglia, Spinal - cytology Ganglia, Spinal - physiology Guinea Pigs Ileitis - chemically induced Ileitis - physiopathology Ileum - innervation Ileum - physiopathology Male Neurons, Afferent - physiology Nociceptors - physiology Patch-Clamp Techniques Potassium - metabolism Potassium Channel Blockers - pharmacology Sodium - metabolism Trinitrobenzenesulfonic Acid
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Summary:	This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12-24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 microm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls (P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group (P < 0.05). The number of action potentials discharged increased in the TNBS group (P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na(+) and K(+) channels at the soma, which persist after removal from the inflamed environment.
ISSN:	0193-1857
DOI:	10.1152/ajpgi.00406.2001