Aim
The role of substance P and the neurokinin-1 receptor (NK-1R) in the transition from inflammation to dysplasia in inflammatory bowel disease is not clear. Materials and
Conclusion
A selective NK-1R antagonist may delay the development of further colonic damage, offering a potential treatment for patients with long-standing colitis.
Methods
Colitis-associated dysplasia was induced in Sprague-Dawley rats by intracolonic, then systemic, administration of trinitrobenzene sulfonic acid. One group of animals received the NK-1R antagonist SR140333; the rest received vehicle. Colons were removed and analyzed for damage and expression of NK-1R downstream components.
Results
The NK-1R antagonist-treated animals had significantly reduced macroscopic and microscopic damage and decreased incidence of inflammatory bowel disease. Twice as many of these animals had a normal diagnosis in any region of the colon. A decrease in proliferation index, Cox-2 expression, and active Erk1/2 was found compared with the vehicle-treated group. In Caco-2 cells, Erk1/2 was activated by substance P and prostaglandin E2.