A Model in Female Rats With Phenotypic Features Similar to Interstitial Cystitis/Bladder Pain Syndrome.

Timothy J Ness,Alan Randich,Cary Dewitte,Jianguo G Gu,Morgan P Hart,Buffie Clodfelder-Miller,Jennifer J Deberry,Jennifer Ling

doi:10.3389/fpain.2021.791045

Abstract

This report describes methodological and exploratory investigations of the zymosan-induced neonatal bladder inflammation (NBI) model of interstitial cystitis/bladder pain syndrome (IC/BPS) in female rats. These results validate and extend the currently employed model by evaluating critical timepoints for obtaining treatment effects and identified that a second insult as an adult including repeat intravesical zymosan, intravesical lipopolysaccharide, acute footshock stress, neuropathic nociception (facial) or somatic inflammation (hindpaw) all resulted in magnified visceromotor responses to urinary bladder distension (UBD) in rats which had experienced NBI when compared with their controls. NBI also resulted in increased tone and reactivity of pelvic floor musculature to UBD, as well as increased responsiveness to intravesical potassium chloride solutions, abnormal anxiety measures (elevated plus maze) and an increased number of submucosal petechial hemorrhages following 30 min of hydrodistension of the bladder. These phenotypic findings have correlates to the clinical features of IC/BPS in humans and so support use of this model system to examine mechanisms of and treatments for IC/BPS.

Highlights

Preclinical models are used to trial potentially effective therapies for painful disorders and to probe mechanisms of these disorders
Voiding Episodes Are More Numerous in Rats Treated With Zymosan on postnatal days 14-16 (P14-16) and P21-23 Data described in Table 1 indicate the Total Number of Voids measured in adult female rats treated with intravesical zymosan on either days P14-16 or P21-23 was statistically greater than the Total Number of Voids in their corresponding neonatal Anesth- control groups which did not experience bladder inflammation (p = 0.003 for P14-16 groups; p = 0.015 for P21-23 groups; unpaired t-test comparisons)
A statistical comparison demonstrated that visceromotor responses (VMRs) to urinary bladder distension (UBD) in the neonatal bladder inflammation (NBI)-acute footshock (AFS) group were more robust than those of the NBI-No FootShock (NFS) group (p = 0.001), the Anesth-AFS group (p = 0.032) and the AnesthAnesth group (p = 0.014)

Summary

Introduction

Preclinical models are used to trial potentially effective therapies for painful disorders and to probe mechanisms of these disorders. A recent scientific panel of the NIH-sponsored multicenter Multidisciplinary Approach to Chronic Pelvic Pain (MAPP) Network [1] identified that non-human animal models of the disorder interstitial cystitis/bladder pain syndrome (IC/BPS) needed to have features of that disorder which included [1] nociception to bladder distension, [2] pelvic nociception and [3] urinary frequency. We have reported that similar bladder inflammation treatments administered at P28-30 [2] or P90-92 [4] did not lead to augmented responses as adults. Those studies gave evidence that there exists a critical developmental period where inflammatory events may alter subsequent sensory processing. VMRs to UBD and spontaneous rates of micturition were both examined

Methods

Results

Discussion

Conclusion