Experimental colitis in mice and sensitization of converging visceral and somatic afferent pathways

Abstract

Chronic pain syndromes affecting different organs often coexist. We hypothesized that sensitization of one afferent pathway may affect converging input from other areas of the body. We induced colitis in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS); control animals were treated with equal volumes of vehicle (50% ethanol) only. Visceromotor responses to graded colorectal distension, cystometrograms, and response thresholds to mechanical and thermal stimulation of both hind paws were determined on days 7 and 14. Inflammation of colon and bladder was assessed with validated histological markers and scores. TNBS caused significant colitis on day 7 that resolved by day 14; there was no evidence of bladder inflammation. There was a significant hypersensitivity to colorectal distension on day 7, which returned to normal on day 14. This was associated with bladder overactivity, as demonstrated by early onset of micturition and more frequent micturition on day 7 after TNBS administration. Colitis also significantly altered responses to mechanical and thermal stimulation of both hind paws on day 7 but not day 14. We conclude that cross talk between afferent visceral and somatic pathways may contribute to the coexistence of pain syndromes.