Study of Pelvic Organ Cross-sensitization

Description of projects available to graduate students:
Recently, our radiation cystitis research lead to the development of a new mouse model for studying pelvic organ cross-sensitization. Cross-sensitization between pelvic organs promotes the transmission of noxious stimuli from an irritated organ to an adjacent structure sensitizing the neurons that innervate both affected and unaffected organs. The colon and the urinary bladder are two pelvic organs that have a high number of convergent afferent neurons and clinically exhibit overlapping symptoms. This may be a major contributing factor to the development of pelvic pain and bladder overactivity. In our model, the descending colon is briefly withdrawn from the abdomen and selectively irradiated without affecting surrounding organs. This approach allows us to induce colitis without instilling inflammatory agents (e.g. TNBS) into the colon that may leak out or be absorbed and enter the circulation thereby directly affecting the bladder and its sphincters. Studies from our laboratory have demonstrated that selective irradiation of the colon results in afferent sensitization and bladder overactivity within 7 days. Our ongoing research is directed to characterization of the time-course and mechanism for the development of bladder-colon cross-sensitization and the resulting bladder overactivity and nociception. Another objective is to identify therapeutic drug targets for the prevention of cross-sensitization.
To characterize bladder pathology following colonic irritation, at different time points after irradiation, cystometry on decerebrated mice are performed following Ussing chamber measurements of transepithelial resistance and histological quantification of mast cells. The other bladders are used for in vitro tension measurements and imaging studies using our unique optical imaging system.

Techniques graduate student will learn:
See above.