Animal Models For Interstitial Cystitis/Painful Bladder Syndrome

ÖZET Animal Models For Interstitial Cystitis/Painful Bladder Syndrome The International Continence Society has defined IC/PBS as “the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology” (1). IC is a chronic inflammation of the urinary bladder in the absence of verified infection (2, 3), and presents with the symptoms of frequent and urgent urination along with pain or irritation in the bladder and lower urinary tract (LUT), necessitating the addition of the new terminology painful bladder syndrome (PBS) (3-5). Complete diagnostic criteria for epidemiological studies of IC/PBS have not been established. Earlier diagnostic criteria proposed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDKK) included a cystoscopic finding of glomerulations upon bladder distension or Hunner’s ulcer, in addition to bladder pain or urinary urgency, along with several criteria to exclude other diseases (6). However, 10% to 34% of patients with urinary urgency due to bladder pain do not exhibit glomerulations upon bladder distension and only 10% of patients diagnosed with IC present with Hunner’s ulcer (7-10). Depending on the diagnostic criteria used, the prevalence of IC/PBS has been estimated as between 0.03% to 2.0% of adults (11-13). The prevalence of IC/PBS among women is estimated to be 2 to 5 times higher than in men (3, 13). The recent Rand Epidemiology study of IC/PBS in women in the United States identified the prevalence of IC/ PBS as 6.5% and 2.7% based on high sensitivity and high specificity diagnostic criteria, respectively, which translates to 3.3 to 7.9 million women suffering from IC/PBS symptoms (14). According to the NIDDK diagnostic criteria, IC/PBS occurs 17 times more frequently in relatives of IC/PBS patients than in the general population in the United States (15). The medical costs have been estimated at more than $100 million per year in the United States (16). IC/PBS patients suffer considerable morbidity over the course of their lives, especially during their most productive years. Advancement in addressing this disease has been painfully slow due to a lack of understanding of the underlying pathophysiology. Etiology of IC/PBS The etiopathogenesis of IC/PBS has not yet been elucidated. Several different theories have been proposed for the underlying pathology of IC/PBS (17), including defects of the barrier glycosaminoglycan layer, infection induced, mast cell activation (18-20) autoimmunity, increased production of antiproliferative factor (21), decreased sialylation and glycosylation of Tam Horsfall Protein (THP) (22), increased TNF-related apoptosis-inducing ligand (TRAIL) receptor 4 (23), elevated transient receptor potential subtype 1 vanilloid receptor in nerve fibers (24), and neuroendocrine and neuroimmune mechanisms (25). The etiopathogenesis of IC/PBS has not yet been elucidatedt. Several different theories have been proposed for the underlying pathology of IC/PBS. Advancement in addressing this disease has been painfully slow due to lack of understanding of the underlying pathophysiology. A main limitation in IC/PBS research has been the lack of an appropriate animal model. In this review, we focused on the current animal models for IC/ PBS disease.