This educational article includes a review of recent investigations into what causes interstitial cystitis/bladder pain syndrome (IC/BPS), with the hope that such a review might help researchers and clinicians appreciate the heterogeneity of IC/BPS; in other words, that it has a variety of causes and mechanisms for development. The authors outline five types of functional changes associated with IC/BPS, including dysfunction of the uroepithelium (urinary tract lining); activation of mast cells, which play a key role in inflammation; autoimmunity, or the mounting of immune response directed at one’s own healthy tissues or cells; urinary tract infections; and inflammation associated with the nervous system. Through careful analysis of different IC/BPS presentations, it may be possible to better define IC/BPS subtypes, each of which may respond better to different types of treatment. Toward that end, it would help to have good biomarkers of IC/BPS, detectable in urine or blood, that match up with the various underlying causes. Although there has been extensive research into IC/BPS biomarkers, as is outlined and reviewed in this article, researchers don’t yet understand them well enough to say for sure that any of them could be used in clinical practice for diagnostic purposes.

When healthy individuals are exposed to painful stimuli, blood flow seems to increase in specific areas of the brain, previous studies have shown. Now, research is suggesting that bladder-related sensations influence cerebral blood flow in women with interstitial cystitis (IC). The study included 11 women with IC who underwent 3 brain scans: one with a full bladder, one with an empty bladder, and one while being subjected to heat-related pain. For comparison, 11 healthy control subjects underwent brain scans under those same conditions. Under full bladder conditions, women with IC had marked increases in blood flow in multiple regions of the brain associated with pain, emotion, and motor control. By contrast, when women with IC were exposed to heat pain or had an empty bladder, there were some increases in brain blood flow, but the result was not much different compared with what was observed in the healthy control subjects. This differences in blood flow in the full bladder state suggests women with IC process bladder-related sensations differently than women without IC. The findings may help researchers better understand how and why women with IC experience pain.

There is rapidly growing interest in looking at the microbiome (i.e., the variety of microorganisms associated with humans) and how certain features of the microbiome could promote health, or be a factor in illness. In particular, some researchers think the microbiome could be implicated in the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Although the exact cause of IC/BPS is still unknown, there are studies suggesting that the microbiome influences pelvic pain in animals; thus, there is speculation that microorganisms in the gut or reproductive tract of humans could be somehow influencing pain symptoms associated with IC/BPS in humans as well. In this article, researchers characterize the microbiome of both IC/BPS patients and healthy control subjects. In all, they found 26 significant features of the IC microbiome, including various groups of organisms that were found more frequently in the stool of IC patients versus controls. The investigators are interested in looking more closely at these features to see if they vary, depending on certain states, such as IC flares or remissions. In the future, knowing the IC microbiome might help clinicians accurately diagnose IC/BPS, and perhaps more importantly, might lead to new treatments that are directly targeted at organisms known to be prevalent in the IC microbiome.

Although the exact cause of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unknown, some researchers believe that certain factors in the urine could be a contributing factor or cause of the condition. This group of investigators previously found that urinary cations (positively-charged ions) are found in higher amounts in patients with IC/BPS compared with control subjects. They also found urinary cations from the IC/BPS patients were more toxic to living cells versus those found in controls; moreover, a substance called Tamm–Horsfall protein (THP) was effective in reducing this excess cytotoxicity. This follow-up report specifically focuses on measurement of these toxic urinary cations in male patients with IC/BPS and whether THP can neutralize them. The investigators collected urine specimens from 51 male patients and 33 male controls and found the cationic content of the urine was significantly higher in the male IC/BPS patients. The cations were more toxic to cells in the IC/BPS patients, and as in the previous study, it was found that THP reduced this toxicity to the level seen in the control subjects. Taken together, these results suggest that these cations might be the cause for bladder dysfunction in patients with IC/BPS, and that a new therapeutic strategy could be explored for potential to relieve bladder symptoms associated with IC/BPS.

The cause of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unclear, though dietary choices and lifestyle factors are often suspected as the cause in some men with the condition. However, there are few studies that comprehensively evaluate the link between diet/lifestyle and this condition. Accordingly, researchers in China recruited 784 men with CP/CPPS from hospitals in Shanghai and evaluated each using a questionnaire that looked at their medical history, diet and lifestyle, CP/CPPS symptoms and more. For comparison, they used the same questionnaire in 785 control subjects (i.e., men without CP/CPPS). When they analyzed the results, researchers found a number of potential diet- or lifestyle-related factors that raised the risk of CP/CPPS, including smoking, drinking alcohol, stress, nightshift work, frequent sexual activity, holding urine, less water intake, and imbalanced diet. Moreover, they found several diet/lifestyle factors associated with severe pain in CP/CPPS patients, including consumption of caffeinated drinks, less water intake, and lack of exercise. These findings encouraged investigators, since so many of them are modifiable (e.g., smoking). However, researchers still don’t know exactly how these factors would cause CP/CPPS or increase pain associated with the condition, suggesting a need for more research.

Avoiding coffee is one effective way to reduce urinary symptoms for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Yet studies of coffee reduction as a strategy to prevent urinary symptoms have yielded conflicting evidence. To clarify the potentially negative effect coffee may have on urinary symptoms, researchers conducted a double-blind study on 49 young, healthy volunteers. These healthy subjects stopped drinking coffee for 5 days, and then, for the next 5 days, consumed either regular or decaffeinated coffee. There were two interesting findings: first, for the subjects who started drinking regular coffee, there was a significant increase in urinary urgency and frequency; in contrast, the group of subjects drinking decaffeinated coffee experienced no such increase in symptoms. Secondly, the researchers looked closer at the subjects’ habits prior to the study–in particular, whether they were frequent or infrequent coffee drinkers. They found that the frequent drinkers had fewer symptoms when re-exposed to regular coffee, while the infrequent drinkers had the largest increase in urinary symptoms. Taken together, these findings suggest that urgency and frequency could be prevented by avoiding regular coffee; moreover, people who are not used to drinking regular coffee might be the ones who are most vulnerable to its potential effects on urinary symptoms.