Animal Models for Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)

Abstract

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).

The mouse cyclophosphamide model of bladder pain syndrome: tissue characterization, immune profiling, and relationship to metabotropic glutamate receptors

“…Therefore, relevant preclinical models are of great importance. For the vast majority of PBS rodent models, employed to date (reviewed in _ Izgi and Daneshgari 2013), micturition dysfunction has been the best characterized functional readout. However, pelvic hyperalgesia, a hallmark of PBS, has been validated only in a few of the models (Robbins et al 2007;Rudick et al 2009;.…”

Pathological and clinicopathological features of canine and feline bladder disease

“…Neurological abnormalities are one of the major hypothesised feature of BPS and FIC. Increased immunoreactivity for substance P, a neurokinin neurotransmitter and increased density of neurokinin-1 receptors has been associated with BPS (173,291). In conclusion, there are a number of biomarkers that could be promising for diagnosis and/or treatment of BPS, however there is likely to be a combination of biomarkers, rather than one single biomarker, that is relevant for disease diagnosis or treatment (178).…”

“…Another proposed pathogenic mechanism for FIC is neurogenic inflammation with increased C-fibre neuron sensitivity, and upregulation of the stress response system (SRS), indicating increased sympathetic activation (72) due to environmental stressors (439,440). Increased immunoreactivity for substance P has been associated with FIC (54,173). Finally, altered acetylcholine synthesis and release in the oesophageal mucosa has been identified in FIC cats, suggesting that systemic cholinergic changes may be involved in altering systemic sensory function and visceral hyperalgesia (38).…”