Citrobacter rodentium colitis evokes post-infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons

AUTOR(ES)

Ibeakanma, Charles

FONTE

Blackwell Science Inc

RESUMO

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 (∼150% increase versus control; P= 0.04). In voltage clamp studies, transient outward (IA) and delayed rectifier (IK) currents were suppressed at day 10 and IA 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 IA 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.

Documentos Relacionados

• Ocular flutter, postural body tremulousness and CSF pleocytosis: a rare post-infectious syndrome.
• EXERCISE CAPACITY IN CHILDREN AND ADOLESCENTS WITH POST-INFECTIOUS BRONCHIOLITIS OBLITERANS: A SYSTEMATIC REVIEW
• Health-related quality of life in post-infectious bronchiolitis obliterans: agreement between children and their proxy
• Citrobacter rodentium, the Causative Agent of Transmissible Murine Colonic Hyperplasia, Exhibits Clonality: Synonymy of C. rodentium and Mouse-Pathogenic Escherichia coli
• Ca2+ sparks and secretion in dorsal root ganglion neurons