Effects of Intravesical Prostaglandin E2 on Bladder Function are Preserved in Capsaicin-Desensitized Rats

2020 ◽  
Author(s):  
James A. Hokanson ◽  
Christopher L Langdale ◽  
Philip H Milliken ◽  
Arun Sridhar ◽  
Warren M. Grill
Keyword(s):  
Perfusion Pressure ◽  
Bladder Capacity ◽  
Female Rats ◽  
Bladder Function ◽  
Prostaglandin E ◽  
Urethral Pressure ◽  
Urinary Urgency ◽  
Hypogastric Nerve ◽  
C Fibers ◽  
Bladder Compliance

Prostaglandin E2 (PGE2) instilled into the bladder generates symptoms of urinary urgency in healthy women and reduces bladder capacity and urethral pressure in both humans and female rats. Systemic capsaicin desensitization, which causes degeneration of C-fibers, prevented PGE2 mediated reductions in bladder capacity, suggesting that PGE2 acts as an irritant (Maggi et al.1988). In the present study, we instilled PGE2 in female rats after capsaicin desensitization, but without the hypogastric nerve transection that was conducted in the Maggi et al. study. One week after capsaicin injection (125 mg/kg, SC) rats underwent cystometric and urethral perfusion testing under urethane anesthesia with saline and 100 µM PGE2. Similar to naïve rats, capsaicin-desensitized rats exhibited a reduction in bladder capacity from 1.24 ± 0.13 ml to 0.70 ± 0.10 ml (P=0.002, n=9), a reduction in urethral perfusion pressure from 19.3 ± 2.1 cmH2O to 10.9 ± 1.15 cmH2O (P=0.004, n=9), and a reduction in bladder compliance from 0.13 ± 0.020 ml/cmH2O to 0.090 ± 0.014 ml/cmH2O (P=0.011, n=9). Thus, changes in bladder function following the instillationof PGE2 were not dependent on capsaicin-sensitive pathways. Further, these results suggest that urethral relaxation/weakness and/or increased detrusor pressure as a result of decreased compliance may contribute to urinary urgency and highlight potential targets for new therapies for overactive bladder.

scholarly journals Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats

2019 ◽  
Vol 316 (4) ◽  
pp. F703-F711 ◽  
Author(s):  
Yan Zhang ◽  
Shun Li ◽  
Todd Yecies ◽  
Tara Morgan ◽  
Haotian Cai ◽  
...  
Keyword(s):  
Bladder Capacity ◽  
Saline Control ◽  
Pelvic Nerve ◽  
Analgesic Agent ◽  
Hypogastric Nerve ◽  
C Fibers ◽  
Pelvic Nerves ◽  
C Fiber ◽  
Bladder Activity

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

GABAergic contribution to rat bladder hyperactivity after middle cerebral artery occlusion

2000 ◽  
Vol 279 (4) ◽  
pp. R1230-R1238 ◽  
Author(s):  
Sayoko Kanie ◽  
Osamu Yokoyama ◽  
Kazuto Komatsu ◽  
Koichi Kodama ◽  
Satoshi Yotsuyanagi ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Receptor Agonist ◽  
Bladder Capacity ◽  
Artery Occlusion ◽  
Female Rats ◽  
Left Middle Cerebral Artery ◽  
Urethral Pressure ◽  
Cerebral Artery Occlusion

To evaluate the influences of γ-aminobutyric acid (GABA) mechanisms on bladder hyperactivity after left middle cerebral artery occlusion, cystometric recordings were obtained from unanesthetized female rats. Intracerebroventricular administration of both muscimol (GABAA receptor agonist; 0.1–10 nmol) and baclofen (GABAB receptor agonist; 0.1–3 nmol) produced dose-dependent inhibitions of micturition with increases in bladder capacity (BC). The effects of high doses (1–10 nmol) were similar in sham-operated (SO) and cerebral-infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABAA receptor antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first decreased and subsequently increased. An increase in urethral pressure was observed after administration of bicuculline (3 nmol) but not with either muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen-treated rats were not significantly different from those of vehicle-treated rats. These results suggest that GABAergic mechanisms inhibit the micturition reflex at the supraspinal level but that this can change as a result of CI.

Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice

2008 ◽  
Vol 295 (2) ◽  
pp. F507-F514 ◽  
Author(s):  
Gerald P. McCafferty ◽  
Blake A. Misajet ◽  
Nicholas J. Laping ◽  
Richard M. Edwards ◽  
Kevin S. Thorneloe
Keyword(s):  
Urinary Bladder ◽  
Potential Role ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Cyclooxygenase Inhibitors ◽  
Prostaglandin E ◽  
Wild Type ◽  
Pathological Conditions ◽  
Freely Moving ◽  
Ep3 Receptor

Nonsteroidal anti-inflammatory cyclooxygenase inhibitors that function to reduce prostaglandin E2 (PGE2) production have been widely reported as effective agents in models of urinary bladder overactivity. We therefore investigated a potential role for the PGE2 receptor, EP3, in urinary bladder function by performing conscious, freely moving cystometry on EP3 receptor knockout (KO) mice. EP3 KO mice demonstrated an enhanced bladder capacity compared with wild-type (WT) mice (∼185% of WT) under control conditions, based on larger voided and infused bladder volumes. Infusion of the EP3 receptor agonist GR63799X into the bladder of WT mice reduced the bladder capacity. This was ineffective in EP3 KO mice that demonstrated a time-dependent increase in bladder capacity with GR63799X, an effect similar to that observed with vehicle in both genotypes. In addition, infusion of PGE2 into WT mice induced bladder overactivity, an effect that was significantly blunted in the EP3 KO mice. The data reported here provide the first evidence supporting a functional role for EP3 receptors in normal urinary bladder function and implicate EP3 as a contributor to bladder overactivity during pathological conditions of enhanced PGE2 production, as reported previously in overactive bladder patients.

scholarly journals Urodynamic evaluation of patients with localized prostate cancer before and 4 months after robotic radical prostatectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Sup Lee ◽  
Seung-ju Lee
Keyword(s):  
Radical Prostatectomy ◽  
Outlet Obstruction ◽  
Maximum Flow ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Detrusor Contraction ◽  
Bladder Compliance ◽  
Urethral Closure ◽  
Relative Change ◽  
Urodynamic Parameters

AbstractRadical prostatectomy can alter the anatomy of the urinary bladder. We aimed to evaluate bladder function before and 4 months after radical prostatectomy using the urodynamic test and overactive bladder (OAB) symptom score. Among 70 prospectively enrolled patients, 61 patients completed the study. In the urodynamic test, bladder capacity and compliance did not change, the frequency of involuntary detrusor contraction decreased, the maximum flow rate and bladder outlet obstruction index improved, and the maximum urethral closure pressure (MUCP) deteriorated. Further evaluation of urodynamic parameters according to changes in symptoms was made. Although change in bladder compliance was correlated with changes in OAB symptoms, not the relative change of bladder compliance but the relative change in the MUCP was reliable factor when OAB symptoms were deteriorated. In general, prostatectomy did not deteriorate the condition of the detrusor; rather, change in the MUCP could be responsible for postprostatectomy OAB.

Acute, severe traumatic spinal cord injury: improving urinary bladder function by optimizing spinal cord perfusion

2021 ◽  
pp. 1-8
Author(s):  
Florence R. A. Hogg ◽  
Siobhan Kearney ◽  
Eskinder Solomon ◽  
Mathew J. Gallagher ◽  
Argyro Zoumprouli ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Urinary Bladder ◽  
Perfusion Pressure ◽  
Bladder Function ◽  
Traumatic Spinal Cord Injury ◽  
Injury Site ◽  
Bladder Compliance ◽  
Cord Injury

OBJECTIVE The authors sought to investigate the effect of acute, severe traumatic spinal cord injury on the urinary bladder and the hypothesis that increasing the spinal cord perfusion pressure improves bladder function. METHODS In 13 adults with traumatic spinal cord injury (American Spinal Injury Association Impairment Scale grades A–C), a pressure probe and a microdialysis catheter were placed intradurally at the injury site. We varied the spinal cord perfusion pressure and performed filling cystometry. Patients were followed up for 12 months on average. RESULTS The 13 patients had 63 fill cycles; 38 cycles had unfavorable urodynamics, i.e., dangerously low compliance (< 20 mL/cmH2O), detrusor overactivity, or dangerously high end-fill pressure (> 40 cmH2O). Unfavorable urodynamics correlated with periods of injury site hypoperfusion (spinal cord perfusion pressure < 60 mm Hg), hyperperfusion (spinal cord perfusion pressure > 100 mm Hg), tissue glucose < 3 mM, and tissue lactate to pyruvate ratio > 30. Increasing spinal cord perfusion pressure from 67.0 ± 2.3 mm Hg (average ± SE) to 92.1 ± 3.0 mm Hg significantly reduced, from 534 to 365 mL, the median bladder volume at which the desire to void was first experienced. All patients with dangerously low average initial bladder compliance (< 20 mL/cmH2O) maintained low compliance at follow-up, whereas all patients with high average initial bladder compliance (> 100 mL/cmH2O) maintained high compliance at follow-up. CONCLUSIONS We conclude that unfavorable urodynamics develop within days of traumatic spinal cord injury, thus challenging the prevailing notion that the detrusor is initially acontractile. Urodynamic studies performed acutely identify patients with dangerously low bladder compliance likely to benefit from early intervention. At this early stage, bladder function is dynamic and is influenced by fluctuations in the physiology and metabolism at the injury site; therefore, optimizing spinal cord perfusion is likely to improve urological outcome in patients with acute severe traumatic spinal cord injury.

Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis

2014 ◽  
Vol 307 (2) ◽  
pp. F234-F241 ◽  
Author(s):  
Kentaro Takezawa ◽  
Makoto Kondo ◽  
Hiroshi Kiuchi ◽  
Tetsuji Soda ◽  
Tetsuya Takao ◽  
...  
Keyword(s):  
Bladder Dysfunction ◽  
Bladder Wall ◽  
Bladder Capacity ◽  
Rapid Decrease ◽  
Bladder Function ◽  
Functional Changes ◽  
Pressure Threshold ◽  
Bladder Compliance ◽  
Conventional Methods ◽  
Voided Volume

Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction.

scholarly journals Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines

2019 ◽  
Author(s):  
Jiajie Jessica Xu ◽  
Zuha Yousuf ◽  
Zhonghua Ouyang ◽  
Eric Kennedy ◽  
Patrick A. Lester ◽  
...  
Keyword(s):  
Heart Rate ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Bladder Pressure ◽  
Anesthetic Depth ◽  
Anesthetic Agents ◽  
Bladder Compliance ◽  
Cord Injury ◽  
Recovery Times ◽  
Bladder Pathology

AbstractUrodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in animal models, especially cats (a common model of spinal cord injury and associated bladder pathology), anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and α-chloralose) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [ΔHR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

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

2017 ◽  
Vol 313 (5) ◽  
pp. F1169-F1177 ◽  
Author(s):  
James A. Hokanson ◽  
Christopher L. Langdale ◽  
Arun Sridhar ◽  
Warren M. Grill
Keyword(s):  
Overactive Bladder ◽  
Prostaglandin E2 ◽  
Perfusion Pressure ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Wistar Rat ◽  
Bladder Compliance ◽  
Urethral Smooth Muscle ◽  
Proximal Urethra ◽  
Promising Avenue

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.

scholarly journals Recruitment of unmyelinated C-fibers mediates the bladder-inhibitory effects of tibial nerve stimulation in a continuous-fill anesthetized rat model

2019 ◽  
Vol 317 (1) ◽  
pp. F163-F171 ◽  
Author(s):  
Jason P. Paquette ◽  
Paul B. Yoo
Keyword(s):  
Overactive Bladder ◽  
Nerve Stimulation ◽  
Tibial Nerve ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Fiber Types ◽  
Percutaneous Tibial Nerve Stimulation ◽  
Inhibitory Effects ◽  
C Fibers ◽  
Tibial Nerve Stimulation

Although percutaneous tibial nerve stimulation is considered a clinically effective therapy for treating overactive bladder, the mechanism by which overactive bladder symptoms are suppressed remains unclear. The goal of the present study was to better understand the role of specific neural inputs (i.e., fiber types) on the bladder-inhibitory effects of tibial nerve stimulation (TNS). In 24 urethane-anesthetized rats, a continuous suprapubic saline infusion model was used to achieve repeated filling and emptying of the bladder. A total of 4 TNS trials (pulse frequency: 5 Hz) were applied in randomized order, where each trial used different amplitude settings: 1) no stimulation (control), 2) Aβ-fiber activation, 3) Aδ-fiber activation, and 4) C-fiber activation. Each stimulation trial was 30 min in duration, with an intertrial washout period of 60−90 min. Our findings showed that TNS evoked statistically significant changes in bladder function (e.g., bladder capacity, residual volume, voiding efficiency, and basal pressure) only at stimulation amplitudes that electrically recruited unmyelinated C-fibers. In a subset of experiments, TNS also resulted in transient episodes of overflow incontinence. It is noted that changes in bladder function occurred only during the poststimulation period. The bladder-inhibitory effects of TNS in a continuous bladder filling model suggests that electrical recruitment of unmyelinated C-fibers has important functional significance. The implications of these findings in percutaneous tibial nerve stimulation therapy should be further investigated.

COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat

2003 ◽  
Vol 284 (2) ◽  
pp. R574-R585 ◽  
Author(s):  
V. Y. Hu ◽  
S. Malley ◽  
A. Dattilio ◽  
J. B. Folsom ◽  
P. Zvara ◽  
...  
Keyword(s):  
Lower Urinary Tract ◽  
Specific Inhibitor ◽  
Female Rats ◽  
Prostaglandin E ◽  
Lower Urinary Tract Function ◽  
Tract Function ◽  
Cox 2 ◽  
Micturition Reflexes ◽  
Lower Urinary

The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H)-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D2-methoxime expression in the bladder was significantly ( P ≤ 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E2 was significantly ( P ≤ 0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis.

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