Citrobacter rodentium colitis evokes post-infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons.
To investigate the possible contribution of peripheral sensory mechanisms to abdominal pain following infectious colitis, we examined whether the Citrobacter rodentium mouse model of human E. coli infection caused hyperexcitability of nociceptive colonic dorsal root ganglion (DRG) neurons and whether these changes persisted following recovery from infection. Mice were gavaged with C. rodentium or distilled water. Perforated patch clamp recordings were obtained from acutely dissociated Fast Blue labelled colonic DRG neurons and afferent nerve recordings were obtained from colonic afferents during ramp colonic distensions. Recordings were obtained on day 10 (acute infection) and day 30 (infection resolved). Following gavage, colonic weights, myeloperoxidase (MPO) activity, stool cultures, and histological scoring established that infection caused colitis at day 10 which resolved by day 30 in most tissues. Electrophysiological recordings at day 10 demonstrated hyperexcitability of colonic DRG neurons (40% mean decrease in rheobase, P = 0.02; 50% mean increase in action potential discharge at twice rheobase, P = 0.02). At day 30, the increase in action potential discharge persisted (approximately 150% increase versus control; P = 0.04). In voltage clamp studies, transient outward (I(A)) and delayed rectifier (I(K)) currents were suppressed at day 10 and I(A) currents remained suppressed at day 30. Colonic afferent nerve recordings during colonic distension demonstrated enhanced firing at day 30 in infected animals. These studies demonstrate that acute infectious colitis evokes hyperexcitability of colonic DRG neurons which persists following resolution of the infection and that suppression of I(A) currents may play a role. Together, these findings suggest that peripheral pain mechanisms could contribute to post-infectious symptoms in conditions such as post-infectious irritable bowel syndrome.
Ibeakanma
Charles
C
Kingston General Hospital, GIDRU Wing, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7.
Miranda-Morales
Marcela
M
Richards
Michele
M
Bautista-Cruz
Francisco
F
Martin
Nancy
N
Hurlbut
David
D
Vanner
Stephen
S
D000200:Action Potentials; D000818:Animals; D044082:Citrobacter rodentium; D003092:Colitis / Q000150:complications / Q000503:physiopathology*; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000503:physiopathology*; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors; D020671:Posterior Horn Cells