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The Effects of Social and Environmental Stimuli in a New Murine Model for Interstitial Cystitis/Painful Bladder Syndrome
Adam Luchey, Dale Riggs, Barbara Jackson, Can Talug, Stanley Kandzari, James Coad, Yara Daous, Dana Point, Morris Jessop, Stanley Zaslau
West Virginia University, Morgantown, WV
Introduction: The treatment and etiology of Interstitial Cystitis (IC) is still unclear. The Objective was to develop a murine model to evaluate the bladder response to environmental stressors, which have been shown to exacerbate IC symptoms.
Materials & Methods: Forty-one BalB/c (6-7 weeks old) were randomized into the Control Group (CG, n=20) and the Chronic Stress Group (CS, n=21) and allowed to acclimatize for two weeks. CS underwent unpredictable, random, chronic stressors daily: succession of light/dark cycles every 15-30 minutes, changes to bedding (removal, being replaced with water, cage tilt), and social stress (cage rotation). After 10 weeks the mice were sacrificed. The bladders were formalin-fixed and paraffin-embedded, then evaluated with light microscopy using H&E, giemsa and PAS to determine weight, mast cells and urothelial thickness. Statistical significance was determined using the non-parametric Mann-Whitney method.
Results: The bladder weight of CG was 39.4+7.41mg compared to CS of 50.08+11.06mg (p<0.001). | | Mean + Std Dev | Median | Min | Max | Urothelial Mast Cells
(per 200x field; p=0.048) | Control (n=20) | 2.57 + 1.28 | 2.40 | 1.00 | 5.00 | | Stressed (n=21) | 1.83 + 1.03 | 1.40 | 0.50 | 4.30 | | | | | | | Detrusor Mast Cells
(per 200x field; p=0.928) | Control (n=20) | 1.02 + 0.67 | 0.90 | 0.00 | 2.63 | | Stressed (n=21) | 1.04 + 0.74 | 0.80 | 0.10 | 2.90 | | | | | | | | Urothelial Thickness μm (p<0.0001) | Control (n=20) | 6.2 + 0.3 | 6.2 | 5.7 | 6.5 | | Stressed (n=21) | 5.6 + 0.3 | 5.7 | 5.3 | 10.0 |
Conclusions: This study demonstrates a murine model exposed to noxious environmental stimuli to produce the clinical features of IC. This can be used to study the pathogenesis and treatment of the human condition. We hypothesize that stressors may exacerbate IC by thinning the urothelium to the peripheral nerve fibers rather than increasing mast cells. Additional directions include response to reversal of stressors, medications including intravesical agents, and the study of neurogenic and biochemical pathways.
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