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 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.
Moore
Beverley A
BA
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada K7L 5G2.
Stewart
Timothy M R
TM
Hill
Ceredwyn
C
Vanner
Stephen J
SJ
D015761:4-Aminopyridine / Q000494:pharmacology; D015746:Abdominal Pain / Q000139:chemically induced / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D006168:Guinea Pigs; D007079:Ileitis / Q000139:chemically induced / Q000503:physiopathology*; D007082:Ileum / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D026902:Potassium Channel Blockers; D014302:Trinitrobenzenesulfonic Acid; D012964:Sodium; D015761:4-Aminopyridine; D011188:Potassium