Although a recent basic research study suggested that intravesical instillation of platelet-rich plasma (PRP) could be a promising future therapy for patients with interstitial cystitis/bladder pain syndrome (IC/BPS), not all evidence is pointing in the same direction. Platelet-rich plasma (PRP) is produced from the subject’s own blood, which is withdrawn and processed to isolate a platelet-rich extract, which is then reintroduced to the body. In the previous study, rabbits with an induced, experimental form of IC were treated with intravesical PRP, which reduced visible bleeding, and increased the mitotic index, which suggested tissue regeneration. However, in this more recent study, female rats were injected with a substance used to induce IC, and some also received intravesical PRP. Investigators found that PRP in fact did not suppress the swelling, bleeding, and inflammation caused by the IC. This finding underscores the need for more study of PRP as a potential treatment for IC.

Visceral pain (or pain that comes from the internal organs) is often the most concerning symptom for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Little is known about what causes visceral pain in IC/BPS, but some researchers think certain neural mechanisms may play a role. Previously, some research groups have shown that the glial cell, a specific type of cell found in the central nervous system, may be implicated in pain associated with damaged nerve fibers; when they are activated, these cells produce inflammatory factors and have other activity that may contribute to development of pain. Accordingly, this group of researchers decided to evaluate the potential role of glial cells in the spine in causing IC/BPS-related pain. Using a rat model of IC/BPS, the researchers were not able to demonstrate activation of microglia cells. However, they did detect activation of astrocytes (star-shaped nerve cells) in the spines of the rats. In addition, they found a marked increase in an inflammatory substance, IL-1β, and determined that the astrocytes were the only source of this release. Based on that, they hypothesized that IL-1β, released from astrocytes, might be a key precursor step that leads to neuronal excitement and pain. There are no immediate clinical implications of these findings; however, these findings may give researchers some incentive to explore inhibition of spinal astrocytes as a new treatment approach for pain related to IC/BPS.

Mammalian target of rapamycin (mTOR) is an enzyme in the body that may contribute to transmission and modulation of pain. Since pain is a hallmark of interstitial cystitis/bladder pain syndrome (IC/BPS), investigators wanted to know more about the relationship between mTOR and this disorder. To do this, they administered an mTOR-blocking drug called rapamycin to rats that had an induced form of interstitial cystitis. By blocking mTOR, the investigators were able to demonstrate a reduction in both pain and bladder hyperactivity. They also tried using a drug that blocks PI3K, an enzyme that is part of the same signaling pathway as mTOR, and once again were able to demonstrate a reduction in pain and bladder hyperactivity. Thus, for the first time, investigators have been able to demonstrate that targeting these pathways could reduce symptoms in this animal model of interstitial cystitis. Although the finding is early, it does seem that targeting this pathway alleviates pain, raising the possibility that one day, drugs that target these molecules could be used to help manage the symptoms of patients with IC/BPS.

Bladder inflammation is likely one of the key contributors to ongoing symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). In this study, investigators looked at intercellular adhesion molecule 1 (ICAM-1), a protein that is thought to have pro-inflammatory effects. Previous studies have shown an enhanced intensity of ICAM-1 in patients with IC/BPS that correlates with the degree of bladder inflammation. To study this further, investigators used a rat model of severe non-bacterial cystitis, which resembles IC/BPS. After inducing severe bladder inflammation in the rats, the investigators treated some of them with an anti-ICAM-1 antibody, while others were treated with celecoxib, which is a non-steroidal anti-inflammatory drug (NSAID) and others received aprepitant, an anti-nausea drug that also has anti-inflammatory effects. They found that the anti-ICAM-1 antibody significantly decreased bladder inflammation and counts of mast cells, which are cells that play an important role in the process of inflammation. Moreover, the effects of the antibody on bladder inflammation were superior to what the investigators observed with both celecoxib and aprepitant. Based on those findings, it’s thought that ICAM-1 may indeed play a key role in bladder inflammation; and thus, drugs targeting ICAM-1 might be useful someday in treating IC/BPS.

Platelet-rich plasma (PRP) is a unique medical procedure that’s most often used for wound and soft tissue healing. In the procedure, the patient’s own blood is withdrawn and centrifuged to isolate a portion of the patient’s blood that is very rich in platelets. That extract is then injected back into the wound tissue. In this very preliminary study, investigators wanted to find out if the PRP technique also could be an effective treatment for interstitial cystitis (IC) or hemorrhagic cystitis, using rabbits as a model. The study included rabbits experimentally given an induced form of cystitis and treated with PRP, while other rabbits did not receive PRP and served as controls. They found that mitotic index (a method for measuring cell proliferation) was increased in the rabbits who received PRP. They also found that the treatment reduced visible bleeding. These results are promising and suggests that PRP could be a potential alternative treatment for IC/BPS. However, this is a very early study and its results would need to be confirmed in subsequent studies of other animal models and humans before it could be considered as an alternate treatment option.

Researchers in this study identified two inflammation-related genes that are more often expressed in patients with bladder pain syndrome (BPS), providing new clues as to how this syndrome might be treated. They found these differences in gene expression by looking at bladder biopsies from 15 women with BPS, and compared those with samples from 15 control subjects who had healthy bladders. They looked at a total of 96 genes associated with inflammation, of which two, known as FGF7 and CCL21, were found to be linked to clinical outcomes. Later, the investigators used laboratory animals to test how the genes work, confirming that CCL21 in particular may play a role in the development of bladder pain. Rats exposed to CCL21 by intravesical instillation had more bladder excitability, among other effects. The investigators suspect these genes may play a role in how BPS develops, and that by targeting them; new treatment strategies could be developed.

Investigators in this study aimed to test whether an experimental treatment known as BAY 58-2667 could have any potential benefit in the management of interstitial cystitis (IC). The treatment is thought to work by activating an enzyme called soluble guanylyl cyclase (sGC) that is implicated in a variety of medical conditions. Investigators studied the effects of BAY 58-2667 in female mice that were injected with another drug that induces cystitis. The investigators found that BAY 58-2667 prevented the changes in urination they saw in mice who did not receive the treatment. A variety of other laboratory markers were tested, and most pointed to the fact that the treatment had favorable effects in this mouse model of IC. Taken together, the findings suggest BAY 58-2667, and other similar agents that activate sGC, might represent a new and encouraging treatment approach for patients with IC, provided much more study is done.

Researchers in this preclinical study sought to characterize the potential benefits of F16357, a novel agent that may have anti-inflammatory effects or other potential benefits in the setting of interstitial cystitis (IC). The agent is one of a class of several agents, known as PAR1 antagonists, that are under investigation in preclinical studies for a variety of conditions. To test F16357, the researchers delivered the compound directly to bladder of rats with an induced form of IC. After exposure to the compound, the rats were found to be virtually free of any damage to the bladder lining. The level of immune reaction to PAR1 was no higher in the bladder tissue of the IC-induced rats than in normal rat bladder tissue. Furthermore, F16357 seemed to block an increase of urine production and voiding frequency. Based on these early but promising results, investigators from this trial think F16357 could be an interesting candidate for further evaluation as treatment for IC.