Animal Models in Overactive Bladder Research

Abstract

Overactive bladder syndrome (OAB) is a symptom-based diagnosis characterised by the presence of urinary urgency. It is highly prevalent and overlaps with the presence of bladder contractions during urine storage, which characterises the urodynamic diagnosis of detrusor overactivity. Animal models are needed to understand the pathophysiology of OAB, but the subjective nature of the symptom complex means that interpretation of the findings in animals requires caution. Because urinary urgency cannot be ascertained in animals, surrogate markers such as frequency, altered toileting areas, and non-micturition contractions have to be used instead. No model can recapitulate the subjective, objective, and related factors seen in the clinical setting. Models used include partial bladder outlet obstruction, the spontaneous hypertensive rat, the hyperlipidaemic rat, various neurological insults and some gene knock-outs. Strengths and weaknesses of these models are discussed in the context of the inherent difficulties of extrapolating subjective symptoms in animals.

A Functional Analysis of the Influence of β3-adrenoceptors on the Rat Micturition Cycle

“…Acute, acetic acid bladder sensitization was performed by switching to continuous intravesical infusion of acid at a pH of 5.5 (Zhang et al, 2003;Yamaguchi and Chapple, 2007;Sadananda et al, 2009;Parsons and Drake, 2011). The change in micturition parameters was observed within minutes of starting the infusion, and the sensitization continued for the remaining duration of the experiment.…”

A Microfluidic System for Testing the Responses of Head and Neck Squamous Cell Carcinoma Tissue Biopsies to Treatment with Chemotherapy Drugs

“…19 The alternative to cellbased methods has been the use of animal models which too have major drawbacks as a number of pathological and physiological pathways can differ from animal to animal, and animal to human, leading to results that cannot be translated to the clinical setting as well as the additional ethical and moral considerations. 14,24 The major biological benefit of microfluidics is the ability to replicate the in vivo environment, which is lost when using traditional macroscopic vessels. Parameters, such as laminar flow, mass transport driven by diffusion rather than turbulence, constant removal of waste products, while maintaining cell-to-cell interactions via paracrine-and autocrine-signaling molecules, can all be incorporated into such devices.…”

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

“…Because of the fact that these are symptom-based disorders, where chronic pelvic/ bladder pain is the cardinal symptom of IC/BPS and OAB is characterized by urinary urgency (1), both of which are impossible to study in a rat, interpretation of findings in animal models of these syndromes deserves careful attention. Therefore, the focus has been on animal models that display multiple, key characteristics of symptoms of human lower urinary tract disorders such as urinary frequency and pelvic/bladder pain (42). The TRPV4 channel has been implicated as a promising target for the IC/BPS and OAB symptom of increased voiding frequency.…”