Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating pain syndrome characterised by a pain, pressure or discomfort perceived to be related to the urinary bladder. Despite its well recognised impact on the patients, the society and the healthcare systems, effective treatments are still lacking for BPS/ ICS. The power of computers can potentially advance BPS/ IC research by analyzing complex biologic data at cellular and molecular levels.
In this study, we have studied the molecular expression of several bioinformatically defined genes in a disease model of rats with BPS/ IC.

A bioinformatic analysis revealed  21 differentially expressed genes (DEG) in patients with and without Hunner’ s lesion disease and controls. Out of the 21 DEGs, 7 (AQP9, CHI3L1, ITGB2, MMP9, MCP1, BTNL2, HLA-DQB1) were selected for further analysis in the animal models. 
BPS/ IC was induced using the Lipopolisaccaride (LPS) and Cyclophosphamide (CYP) models in rats. Female rats at reproductive age received 1 mg/ml of LPS from E. Coli intravesically for the LPS group (n=8) and 75 mg/kg cyclophosphamide intraperitoneally for the CYP group (n=8) on days 0, 3 and 5.  An intravesical (n=6) and intraperitoneal (n=3) injection of PBS groups were also used. Experiments ended on day 7 and the bladder tissues were removed. After gross examination tissues were cut into half and sent for histologic and molecular analysis.

Gross examination of the bladder tissues confirmed thickened bladder Wall with inflammed mucosa and hemorrhagic areas and areas with increased vascularity in LPS and CYP groups, compared to controls.   Hematoxylin-eosin stained sections showed focal acute inflammation in 2 members of the LPS group (Figure 1A) focal suburothelial hemorrhage and denudation in 4 members of the CYC group (Figure 1B).
Gene expression with PCR showed a model dependent expression of the selected genes. In the LPS group, expression of all genes, except HLA-DQB1, was higher compared to control. Whereas in CYC group, expression of the genes were lower or did not change compared to controls (Figure 2). It appears that intraperitoneal administration of CYC in rats, led to a decrease in the expression of these genes suggesting an supressive effect on the immune system and therefore is not a suitable model for studying inflammatory markers in this disease. In the LPS model, the inflammation appears to be triggered locally via administration of the bacterial LPS into the bladder.

Genes coding surface markers of inflammatory cells have been found to be expressed differently in the two most commonly used animal models representing Hunner lesion disease BPS/ IC. This highlights the importance of meticulous use of animal models in BPS/ IC research.  In case of Hunner lesion disease, both CYC and LPS models reproduce bladder inflammation in gross examination however there is a distinct difference in expression of some immunological markers.

We have demonstrated a model dependent difference in expression of investigated adhesion molecules  that have previously been studied as promising biomarkers.