Research shows bladder pain syndrome patients show changes in gene expression
Bladder pain syndrome, or interstitial cystitis, is a chronic condition characterised by a number of symptoms, including unexplained bladder pain and the feeling of constantly needing to urinate. Two researchers from the University Hospital of Bern have been investigating the roots of this common affliction at a molecular level in an attempt to work out what the causes of the many symptoms associated with this problem are.
Bladder pain syndrome (BPS) was once considered to be a rare condition, but recent statistics have shown it be far more common than previously thought, with at least 230 confirmed cases per 100,000 females and an estimated occurrence of up to 20% of all women. Symptoms include pain in the bladder region, often waking up to urinate and having to go to the toilet a lot in general. BPS is far more common in women, with a ratio of approximately five to one female to male sufferers.
"The full blown disease can be quite debilitating," says Professor Fiona Burkhard. "If you have to go the toilet every fifteen minutes despite having an almost empty bladder, then you have a problem which can majorly impact on your quality of life."
One hypothesis for BPS concerns the epithelial lining that surrounds the bladder. This layer of cells has a number of functions, including stretching to allow for different volumes of urine, sensing and excreting proteins, and forming a barrier that stops any urine - which has high salt levels and thus can have a caustic effect on tissue - from escaping the bladder.
"When looking at patients with BPS, we often see microscopic ulcers throughout the epithelial layer, which suggest that the layer has been compromised as a barrier. If this theory is correct, and the pain is being caused by this, then you might expect to see changes in expression of components that make these epithelial cells impermeable to urine."
These changes have indeed been observed, and the question being asked now is why this is happening. The investigation has narrowed its sights on a class of regulatory molecules called microRNAs - tiny non-coding RNAs involved in the regulation of gene expression. "We have identified a number of these microRNAs which are found at different levels than normal in sufferers of BPS. This change in expression is reflected by changes in the expression of the target proteins."
In a recent paper, the microRNA known as miR-199a-5p was shown to be upregulated in sufferers of bladder pain syndrome. "Too much of this miRNA has an effect on the proteins that help to keep the epithelium watertight, causing it to become more permeable," says Dr Katia Monastyrskaya. "We were able to test this by introducing specific molecules into primary cultures of epithelial cells, and then watching how the cells differentiated and tightened."
Another related problem is bladder over-activity. Essentially the same as BPS but without the perceived pain, the researchers are looking at the differences between over-active bladder with and without obstruction at the gene expression level. "We already have a lot of knowledge on BPS, and we are hoping that by looking at patients with over-active bladders we might be able to single out exactly what component causes the pain using an evidence comparison study.
"The other issue with bladder over-activity is that you can prescribe drugs such as antimuscarinics, but after a year most patients have to stop taking them due to side-effects or because the drugs stop working," says Monastyrskaya. "Therefore, if we can help to single out exactly what the root of over-activity is, we might be able to help."
One of the biggest problems with BPS is the variety of causes, according to Burkhard. "If you don't know what's causing the problem, you have to try various treatments on the patient. It is basically a case of guesswork until you find something that works, and only sometimes does this cause a permanent improvement.
"People can sometimes be in such a miserable state that we end up having to remove their bladder, but sometimes even this does not completely stop the pain," continues Burkhard. "That is one the main issues with BPS; it is one of these classically enigmatic disorders that not a lot is known about, and so it is actually just as much a diagnostic problem as it is a treatment problem."
Funding for Burkhard and Monastyrskaya's work was provided by the Swiss National Research Foundation, and they count themselves lucky to have received it. "Finding funding for non-cancer based research can be difficult to come by, although some of the illnesses that come under this bracket are extremely debilitating," says Burkhard. "We feel it is important to bring awareness to problems such as BPS that don't have the same sort of attention and research time devoted to them as more well-known afflictions."