Stress may play 'critical role' in OAB, IC/PBS

January 1, 2010

Stress is a key component of functional urinary tract disorders and plays a critical role in the exacerbation, and perhaps development, of urinary tract conditions such as overactive bladder and interstitial cystitis/painful bladder syndrome (IC/PBS).

Key Points

San Francisco-Stress is a key component of functional urinary tract disorders and plays a critical role in the exacerbation, and perhaps development, of urinary tract conditions such as overactive bladder and interstitial cystitis/painful bladder syndrome (IC/PBS), according to a study presented at the International Continence Society annual meeting.

In this preliminary study, UCLA investigators set out to characterize changes in micturition frequency, anxiety-related behavior, bladder pathology, and gene expression in rats after exposure to water avoidance (WA) stress.

Twenty-four adult female Wistar rats, a strain genetically predisposed to enhanced anxiety, were exposed to WA stress-a potent psychological stressor associated with heightened elevations of stress hormones-or sham.

"We suspected a similar effect on the urinary tract," said first author Ariana L. Smith, MD, a female urology fellow at UCLA at the time of the study, working with Larissa V. Rodriguez, MD, and colleagues.

In this study, rats were placed on top of a small glass pedestal in a plastic container filled with water for 1 hour each day for 10 consecutive days. Sham rats were also placed on a pedestal, but their containers remained dry.

Immediately following each protocol, the animals were moved to a metabolic cage for a 2-hour voiding assessment, including frequency of urination, voiding intervals and volume, and a fecal pellet count. Urine norepinephrine levels were determined by enzyme-linked immunoabsorbent assay on days 1 and 10, which were deemed to represent acute and chronic stress, respectively. All assessments were compared to baseline values.

Four animals were sacrificed on day 10, their bladders harvested, and bladder tissue histologically examined for structural changes. CD-31 antibody immunofluoresence was used to quantify angiogenesis in the tissue. RNA was extracted, and real-time polymerase chain reaction was used to quantify gene expression.

The remaining eight animals in each group underwent repeat voiding assessments every 3 to 4 days for a month, with repeated WA stress or sham for 10 days before the bladder of each animal was harvested and tested.

The team found that stress-exposed rats developed persistent and significant changes in micturition parameters, including increased urinary frequency and decreases in latency to first void, voiding interval, and volume of first void (approximately half in the stressed animals). They noted that changes in micturition parameters persisted for at least 1 month after the stress protocol ended. In addition, the stressed rats expressed anxiety-like behavior, enhanced fecal pellet excretion, and increased bladder angiogenesis.

In addition, gene expression data showed a trend toward lower expression of nerve growth factor and significantly lower expression of brain derived neurotrophic factor (BDNF) in the stressed animals, suggesting possible links between stress, depression, and decreased expression of BDNF, a finding the team said warrants follow-up studies.

"This appears to be very promising early data, suggesting that this work may represent a novel animal model for studying PBS and OAB," said Dr. Smith, currently an assistant professor of urology at the University of Pennsylvania, Philadelphia. "The robust and long-lasting alterations and end-organ changes connecting stress to pathological findings in this study may provide insight into the pathophysiology of complex voiding disorders."