Abstract: PD70-01
Sources of Funding: The NIH Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP, DK082370) Research Network to LV Rodriguez.

Introduction

Chronic emotional stress plays a role in the exacerbation and possibly the development of functional lower urinary tract disorders. Chronic water avoidance stress (WAS) in rodents is a model with high construct and face validity to bladder hypersensitivity syndromes, such as interstitial cystitis/bladder painful syndrome (IC/BPS), which manifest as urinary frequency and bladder hyperalgesia, which have been shown to be highly responsive to stress. Given the significant overlap of the brain circuits involved in stress, anxiety, and micturition, we evaluated the effects chronic stress has on bladder function and its effects on regional brain activation during bladder filling.

Methods

16 adult female Wistar-Kyoto rats were randomized to 10-day WAS (n=8) or handled controls (n=8). On day 11, rats were evaluated by visceromotor reflex (VMR) for bladder hyperalgesia. VMR was obtained during isotonic bladder distention (0-40 cmH2O) with urethral occlusion. Cerebral perfusion was assessed during bladder distention (20 cmH2O) using [14C]-iodoantipyrine autoradiography with regional cerebral blood flow-related tissue radioactivity (rCBF) analyzed in 3-D reconstructed brains with statistical parametric mapping.

Results

At 20 cmH2O, VMR significantly increased in WAS compared to controls. WAS animals compared to controls showed greater activation in cortical regions of the central micturition circuit, with seed analysis showing increased functional connectivity of the cingulate to the parabrachial/Barrington nucleus complex (PBN), of the PBN to the thalamus and somatosensory and retrosplenial cortices, and of posterior insula to anterior secondary motor cortex.

Conclusions

The current study demonstrates how stress exacerbation of symptoms seen in the majority of patients with IC/PBS may be centrally mediated and gives us anatomic sites to further evaluate the biological mechanisms by which stress may induce or maintain bladder hyperalgesia and urinary frequency as well as a translational model to evaluate the molecular changes behind the brain differences seen in patients with IC/BPS. Collectively, our physiologic and brain mapping results suggest hypersensitivity during bladder filing in WAS animals, as well as increased engagement of portions of the micturition circuit responsive to urgency and the perception of bladder fullness, including viscerosensory perception and its relay to motor regions coordinating imminent bladder contractions.

Funding

The NIH Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP, DK082370) Research Network to LV Rodriguez.