OAB without an overactive bladder in the acute prostaglandin E2 rat model

Abstract

Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a "strong urgency sensation" in healthy women. However, the mechanism by which this occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 µM PGE2 was administered intravesically during open, single-fill cystometry with simultaneous measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2 was also applied to the urethra or bladder selectively by use of a ligature at the bladder neck before (urethra) or during (bladder) closed-outlet, single-fill cystometry. Additional tests of urethral perfusion with PGE2 were made. PGE2 decreased bladder capacity, increased voiding efficiency, and increased sphincter EMG during open cystometry compared with saline controls. The number of nonvoiding contractions did not change with PGE2; however, bladder compliance decreased. During closed-outlet cystometry, PGE2 applied only to the bladder or the urethra did not decrease bladder capacity. Urethral infusion of PGE2 decreased urethral perfusion pressure. Taken together, these results suggest that intravesical PGE2 may decrease bladder capacity by targeting afferents in the proximal urethra. This may occur through urethral relaxation and decreased bladder compliance, both of which may increase activation of proximal urethra afferents from distension of the proximal urethra. This hypothesis stands in contrast to many hypotheses of urgency that focus on bladder dysfunction as the primary cause of OAB symptoms. Targeting the urethra, particularly urethral smooth muscle, may be a promising avenue for the design of drugs and devices to treat OAB.

Detection of Bladder Contractions From the Activity of the External Urethral Sphincter in Rats Using Sparse Regression

“…These findings suggest that one of the effects of PGE2 is to change in the relationship between EUS EMG activity and bladder pressure during contraction. This finding is consistent with previous results showing that PGE2 resulted in reduced bladder capacity [6],[24]. The average NRMSE for all out-of-sample trials obtained was 16.12 ± 6.11 (mean ± standard deviation).…”

“…When using post-PGE2 trial data for training and other post-PGE2 trials for testing, we obtained a significantly more accurate model, in terms of RMSE, than using pre-PGE2 trials for training. This finding suggests that PGE2 administration alters the relationship between EUS EMG activity and bladder pressure, a conjecture supported by previous experimental work [6],[24]. This finding also highlights the importance of preserving the temporal order of the trials to evaluate prediction accuracy.…”

Real-Time Bladder Pressure Estimation for Closed-Loop Control in a Detrusor Overactivity Model

“…Elevated heart rates resulted in some trials being ended prematurely. Although additional resting time between trials was given in order to return the stability of vitals, an alternate simulated OAB model such as the use of Prostaglandin E2 (PGE2) might have better clinical relevance [31]. We made an effort to keep the number of saline and acetic acid trials consistent across different experiments, however we were limited by experimental and anesthetic factors in some cases.…”

Increased bladder sensation without detrusor overactivity revisited: Use of a five‐grade sensory measure

“…Similarly, we only performed urodynamic test once in each patient, with a stable infusion rate of 50 mL/min, although we did not clarify test–retest reproducibility without comparing different infusion rates. We did not perform video‐urodynamics either; therefore, we could not detect smooth urethral sphincter function; still, none of our subjects was revealed to have uninhibited sphincter relaxation during storage by striated sphincter EMG. IBS without DO has clinical significance since it affects the quality of life in patients .…”