Animal models of interstitial cystitis/bladder pain syndrome

Abstract

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic disorder characterized by pelvic and/or bladder pain, along with lower urinary tract symptoms that have a significant impact on an individual’s quality of life. The diverse range of symptoms and underlying causes in IC/BPS patients pose a significant challenge for effective disease management and the development of new and effective treatments. To facilitate the development of innovative therapies for IC/BPS, numerous preclinical animal models have been developed, each focusing on distinct pathophysiological components such as localized urothelial permeability or inflammation, psychological stress, autoimmunity, and central sensitization. However, since the precise etiopathophysiology of IC/BPS remains undefined, these animal models have primarily aimed to replicate the key clinical symptoms of bladder hypersensitivity and pain to enhance the translatability of potential therapeutics. Several animal models have now been characterized to mimic the major symptoms of IC/BPS, and significant progress has been made in refining these models to induce chronic symptomatology that more closely resembles the IC/BPS phenotype. Nevertheless, it's important to note that no single model can fully replicate all aspects of the human disease. When selecting an appropriate model for preclinical therapeutic evaluation, consideration must be given to the specific pathology believed to underlie the development of IC/BPS symptoms in a particular patient group, as well as the type and severity of the model, its duration, and the proposed intervention’s mechanism of action. Therefore, it is likely that different models will continue to be necessary for preclinical drug development, depending on the unique etiology of IC/BPS being investigated.

Interstitial cystitis—an imbalance of risk and protective factors?

“…More recent models instill different noxious compounds, such as protamine sulfate, cyclophosphamide (intraperitoneally), acids, zymosan, and LPS, which can increase urothelial permeability, induce an inflammatory response, alter visceromotor responses, and inflict acute pain depending on the compound and dose. Additionally, treating neonatal rats with zymosan increased bladder plasma extravasation and urinary frequency in them as adults, demonstrating that neonatal bladder injury, an adverse early life experience, can increase urothelial permeability and bladder sensitivity in adults subjected to injury early in life ( 3 ).…”

“…Animal models of RLA include WAS, social defeat, and various other threat-inducing events. Each has been tested in rodents of different ages, sexes, and strains, resulting in various LUTS, and each has advantages and disadvantages for understanding IC ( 2 , 3 ).…”

“…Complex interactions between facilitating and inhibitory neuronal networks in the central nervous system (CNS) influence these perceptions ( 85 , 86 ). These complex CNS interactions appear to be present in humans with chronic primary pain conditions like IC ( 85 , 87 ) and have been reported in rodent models of IC ( 3 ).…”

“…Models of predisposing risk factors like ELA are relevant because ELA is common among humans and cats, and childhood maltreatment is a particularly potent risk factor for IC (102). In the United States, at least 1 in 7 children experienced child abuse or neglect in 2020 2 , and about 1 in 20 boys and 1 in 4 girls experience sexual abuse during childhood 3 . This terrible prevalence is similar to the reported worldwide pooled overall rate of 21%-27% (188).…”

“…Interstitial Cystitis (IC) presents as a chronic painful condition with variable combinations of social, psychological, and biological problems depending on the species and individual patient. In addition to afflicting humans, IC occurs commonly in pet cats ( Felis catus ), is studied in rodent models, and has been reported sporadically in other mammals, including cheetahs, dogs, llamas, and pot-bellied pigs ( 1 – 3 ). This article will focus mainly on humans, cats, a naturally occurring model for IC in humans, and induced rodent models of IC because there is a paucity of information available about other species.…”