Stress changes bladder via HPA axis

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ICS 2009 - The effect of acute and chronic stress and anxiety-like behaviour on bladder motor and sensory function

Tuesday, 06 October 2009

SAN FRANCISCO, CA, USA (UroToday.com) - Stress has been felt to play a role in the exacerbation of urinary tract disorders including painful bladder syndrome (PBS) and overactive bladder (OAB). To better understand the mechanism underlying this relationship, the authors aimed to characterize changes in micturition, anxiety-related behavior and bladder pathology in rats exposed to water avoidance stress (WAS), a potent psychological stressor.

24 adult female Wistar rats were subjected to WAS or sham procedure 1 hour a day for 10 consecutive days. Rats were placed on a glass platform in the center of a plastic container filled with water. In the sham group, the plastic container was left empty. The number of fecal pellets excreted while in the container was counted as a measure of stress induced colonic motility. Immediately after day 1 (acute stress or sham) and day 10 (chronic stress or sham), rats were placed in a metabolic cage for a two hour voiding assessment. Urine norepinephrine (NE) levels were determined by ELISA on days 1 and 10. Fecal pellet excretion, voiding parameters and NE levels were compared to baseline values obtained prior to stress intervention. To quantify anxiety-like behavior video-recording of a light-dark box (LDB) transition test was obtained. Animals were placed in the brightly illuminated section and allowed to move freely back and forth to the dark chamber for 10 minutes. Coding of stressful behavior allowed comparison of the two groups. Four animals from each group were sacrificed on day 10; bladders were harvested, compared histologically, treated CD-31 antibody to assess angiogenesis, and RNA was extracted for real-time PCR. The remaining 8 animals in each group underwent repeat voiding assessment every three days for one month, repeat WAS or sham for 10 days, and bladder harvest for angiogenesis quantification and RNA extraction. The authors found that rats exposed to WAS developed a significant increase in micturition frequency and decrease in latency to first void, voiding interval and volume of first void when compared to sham animals and to baseline voiding parameters of all animals. Alteration in micturition parameters following the termination of the stress protocol persisted for approximately one month. Stressed rats also showed increased fecal pellet excretion and anxiety-like behavior consistent with prior studies. Additionally, bladder specimens from stressed animals revealed increased angiogenesis and decreased brain derived growth factor (BDGF) expression when compared to sham animals. No detectable difference in urinary NE levels was found.

The authors concluded that psychological stress in rats results in a robust and long lasting alteration of micturition parameters. The response appears to be related to hypothalamic-pituitary axis activation secondary to stress, resulting in end organ functional manifestations as well as changes in tissue expression and angiogenesis. Similar effects previously reported on the gastrointestinal system together with these findings argue for initiation of this response centrally. They presented a novel model of urinary frequency in the rat subjected to WAS; this model may represent a valid tool for studying PBS and OAB.

Presented by Ariana L. Smith, MD in a session moderated by Clare Juliet Fowler, MD and Sender Herschorn, MD at the International Continence Society (ICS) 39th Annual Meeting - September 29 - October 3, 2009 - Moscone Convention Center - San Francisco, CA, USA