Vol. 282, Issue 6, G1045-G1051, June 2002
TNBS ileitis evokes hyperexcitability and changes in
ionic membrane properties of nociceptive DRG neurons
Beverley A.
Moore,
Timothy
M. R.
Stewart,
Ceredwyn
Hill, and
Stephen J.
Vanner
Gastrointestinal Diseases Research Unit, Queen's
University, Kingston, Ontario, Canada K7L 5G2
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 µm). 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.
sensory neurons; small intestine; abdominal pain; inflammation; peripheral sensitization; trinitrobenzene sulfonic acid; dorsal root
ganglia