Urologic Diseases Research Updates
Fall 2009
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.
IC/PBS
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.
Hypersensitivity
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-toread
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
December 2009
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