Urologic Diseases Research Updates
Scientists Devise New Animal Model for Studying Painful Bladder Syndrome
Painful bladder syndrome (PBS) and interstitial cystitis (IC)-often referred to as IC/PBS-are similar conditions that cause recurrent pain in the bladder and pelvic region. Recently, researchers at the University of Alabama reported a potential new rat model for studying bladder hypersensitivity related to IC/PBS. The research, which was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published in the July 2009 issue of The Journal of Urology.
"This model of hypersensitivity, which is produced by bladder inflammation during a critical period of development (the neonatal period), may have usefulness in studies of novel therapy for PBS/IC," wrote Alan Randich, Ph.D., the director of the University of Alabama's behavioral neuroscience Ph.D. program in psychology, and co-authors.
PBS is a general term to describe painful urinary symptoms that cannot be attributed to other sources, such as infection or urinary stones. IC is similar to PBS but has more stringent diagnostic criteria. In addition to pain, which varies from mild to severe, symptoms include urgent and frequent urination.
Scientists do not know what causes IC/PBS, and doctors often have difficulty recognizing IC/PBS because symptoms vary and overlap with other conditions such as overactive bladder. As a result, IC/PBS has been a challenge to study, and effective treatments are slow in coming.
One plausible explanation for IC/PBS, according to Randich and colleagues, is that bladder inflammation during childhood causes hypersensitivity of nerves in the tissues lining the bladder wall, called the urothelium. Urinary tract infections, which are four times more common among girls than boys, are a likely source of bladder inflammation early in life. Adult IC/PBS patients, according to a recent survey, reported experiencing more urinary tract infections and other urinary symptoms indicative of bladder inflammation as children and adolescents.
To test their theory, the scientists administered zymosan-a substance known to cause inflammation-to female rats' bladders via the urethra for 3 consecutive days, beginning 2 weeks after birth. When the rats grew to adulthood, the scientists perfused the rats' bladders with ice-cold saline-a technique known as ice water testing (IWT), used to assess bladder hypersensitivity-and measured nerve activity of the bladder using electromyography (EMG).
Rats who as juveniles received zymosan treatment showed a greater EMG response to IWT compared with controls, indicating the presence of bladder hypersensitivity. Because rats subjected to zymosan as adults showed no enhanced bladder sensitivity, the study's results suggest bladder inflammation at a young age somehow alters the development of nerves in the bladder.
IWT in adults with IC/PBS evokes a response similar to that seen in rats, noted Randich and co-authors, who cited a 2006 report by Mukerji, et al., in which more than 75 percent of participants with IC/PBS reported pain with IWT. In that study, IWT also appeared to distinguish IC/PBS from similar bladder disorders, such as overactive bladder.
Because responses among rats so closely paralleled those of IC/PBS patients, Randich and co-authors believe their system will serve as an important model for studying the relationship of childhood bladder inflammation to IC/PBS.
The National Kidney and Urologic Diseases Information Clearinghouse, an information dissemination service of the NIDDK, has easy-to-read booklets and fact sheets about IC/PBS and other urologic conditions. For more information, visit www.urologic.niddk.nih.gov.
NIH Publication No. 10-5743