Presentation Authors: Tetsuichi Saito*, Shinsuke Mizoguchi, Masahiro Kurobe, Jianshu Ni, Daisuke Gotoh, Pradeep Tyagi, Pittsburgh, PA, Osamu Ishizuka, matsumoto, Japan, Naoki Yoshimura, Pittsburgh, PA
Introduction: Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) is a disease that causes pelvic pain and lower urinary tract symptoms. Psychological stress has been proposed as a factor inducing or worsening BPS/IC symptoms. Accordingly, an animal model of psychological stress induced by water avoidance stress (WAS), which exhibits pelvic pain and urinary frequency, has been proposed as a useful model to study the BPS/IC pathophysiology. Previous studies have also shown that nerve growth factor (NGF) that is known to cause sensitization of nociceptive afferent pathways is increased in the bladder of BPS/IC patients and that urothelial intercellular distance in WAS rats is increased. Thus, in this study using WAS rats, we examined bladder function, pain sensation and expressions of NGF, junction molecules and TRP channels in bladder mucosa.
Methods: Female Wistar rats were divided into the WAS group, which underwent 1-hour WAS for 10 days, and the control group without WAS. All rats then underwent cystometry with intravesical infusion of low dose protamine sulfate (LD-PS) (10mg/ml), which reportedly does not cause changes in bladder activity in normal rats. In separate groups of WAS or control rats, bladder pain behavior after intravesical infusion of LD-PS was evaluated. After the experiments, bladder tissues were harvested for RT-PCR and ELISA analyses. Bladder sections were also evaluated histologically to see the degree of damage caused by PS.
Results: Control rats did not show changes in inter-contraction intervals (ICI) whereas WAS rats showed a significant decrease of ICI after LD-PS infusion (Fig: A). WAS rats also showed a significant increase in PS-induced bladder pain behaviors compared to controls (Fig: B). In bladder mucosa of WAS rats, NGF protein and TRPV1/TRPA1 mRNA levels were increased whereas mRNA levels of junction molecules (Cx43, ZO-1) were decreased (Fig: C&D). Histological evaluation showed the bladder epithelial damage with LD-PS in WAS rats, but not in control rats.
Conclusions: Psychological stress due to WAS increased urinary frequency and bladder pain sensation after LD-PS infusion. WAS-induced NGF upregulation and decreases of junction molecules in bladder mucosa may contribute to the increased susceptibility to bladder insults leading to the urothelial damage.