Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

The effect of pelvic floor muscle training in men with benign prostatic hyperplasia and overactive bladder.

BACKGROUND: Men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH), will have deterioration in the quality of life. OBJECTIVE: The aim of this study was to evaluate the effect of combining pelvic floor muscle training with the urgency suppression technique (PFMT-st) and silodosin in comparison with silodosin in men with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) after 12 weeks of treatment. PATIENTS AND METHODS: A total of 158 patients were randomized into two groups. The control group received oral silodosin at a daily dose of 8 mg. The experimental group was administered PFMT-st and silodosin. The evaluation methods included the number of voids and intensity of urgencies over 24 h using a micturition diary, the International Prostate Symptom Score (IPSS), the Overactive Bladder Questionnaire (OAB-q), and the patient global impression of improvement (PGI-I). RESULTS: 142 of 172 (86.6%) men were assessed (70 in the control group, 72 in the experimental group). The significant changes were in favor of the experimental group (p < 0.001) in the number of voids per 24 h (- 1.95 ± 1.94 vs. - 0.90 ± 1.44), the OAB-q symptom score (- 14.25 ± 10.05 vs. - 9.28 ± 10.60), the intensity of urgencies (- 0.97 ± 0.53 vs. 0.24 ± 0.57), the IPSS (- 4.59 ± 3.00 vs. - 2.30 ± 3.63), and in the PGI-I (2.24 ± 0.79 vs. 3.60 ± 0.92). CONCLUSIONS: The addition of PFMT-st to silodosin treatment significantly improved OAB in men with BPH. This is the first study to confirm that PFMT-st should be the first-choice treatment for OAB in BPH.

[Drug therapy targeting angiotensin II type 1 receptors in brain against frequent urination].

The production of angiotensin II (Ang II) in the brain plays important roles as neurotransmitter and neuropeptide. Central Ang II is involved in regulating various physiological processes, such as blood pressure and water homeostasis, via Ang II type 1 (AT1) receptors. We have demonstrated that Ang II induces frequent urination via AT1 receptors in the brain even at doses that does not seem to affect the blood pressure in animal experiment. Intracerebroventricular administration of Ang II was also found to reduce the bladder capacity without affecting the maximum voiding pressure, post voiding residual urine volume or voiding efficiency. Additionally, the activation of AT1 receptor downstream signal pathway (phospholipase C/protein kinase C/NADPH oxidase/superoxide anion) and suppression of GABAergic nervous system in the brain are involved in the mechanism underlying the central Ang II-inducted frequent urination. AT1 receptor blockers (ARBs) have been widely used to treat hypertension. We demonstrated that peripherally administered ARBs telmisartan, which can penetrate blood-brain barrier, exerted an inhibitory effect on central Ang II-inducted frequent urination. We present the possible drug therapy targeting AT1 receptors in the brain against frequent urination on the results obtained from our recent research work.

Agreement between the visual analogue scale (VAS) and the dysfunctional voiding scoring system (DVSS) in the post-treatment evaluation of electrical nerve stimulation in children and adolescents with overactive bladder.

INTRODUCTION: Electrical nerve stimulation is one of the most commonly used and well-tolerated treatments for overactive bladder (OAB); however, different studies have used different instruments to assess patients' response to treatment. OBJECTIVE: To analyze agreement between use of the visual analogue scale (VAS) and the Dysfunctional Voiding Scoring System (DVSS) for assessing improvement in urinary symptoms following electrical nerve stimulation treatment in children and adolescents with OAB. STUDY DESIGN: A cross-sectional analytical study including children and adolescents of 4-17 years of age diagnosed with OAB who underwent 20 sessions of transcutaneous (TENS) or percutaneous (PENS) electrical nerve stimulation. The DVSS and the VAS were used to assess daytime urinary symptoms before and following treatment. While the DVSS was always applied by a physician, the VAS was applied separately by a physiotherapist and then by a physician. Treatment was considered successful when the DVSS score was zero and the VAS score was ≥90%. Correlations between post-treatment VAS and DVSS scores were evaluated using the kappa coefficient. The VAS scores evaluated by the different professionals were compared for agreement using intraclass correlation and the Bland-Altman plot. RESULTS: Data from 49 cases were available for analysis. Of these, 27 (55.1%) were girls. Mean age was 7.1 ± 2.6 years. There was agreement between the two instruments used, the DVSS and the VAS, in 36/49 patients (73.5%), with a moderate Kappa of 0.44. There was moderate agreement between the VAS scores applied by the two different professionals. DISCUSSION: imitations of the present study include the small sample size and the fact that the inter-observer evaluation was conducted following a single sequence, i.e. all the patients were first evaluated by the physiotherapist and then by the physician, which may have biased answers and the post-treatment VAS scores. Furthermore, although the child participated actively in completing the questionnaires, in cases of divergent answers, the questions were redirected to the responsible adult, and the final answer may not fully represent the patient's true situation. CONCLUSION: The present study found moderate agreement between the DVSS and the VAS, and moderate agreement between VAS scores when the instrument was applied by two different professionals. Although both tools appear to be important, and possibly complementary, a DVSS score of zero precludes the need to apply the VAS.

Defining urge as an uncontrolled micturition explains pathogenesis, informs cure and helps solve the burgeoning OAB crisis.

BACKGROUND: Parallel with the demographic ageing crisis, is a disabling overactive bladder (OAB) crisis (urgency/frequency/nocturia), 30% prevalence in older women, pathogenesis stated as unknown and, according to some learned societies, incurable. HYPOTHESIS/AIMS: To review International Continence Society and Integral System paradigms to test our thesis that OAB per se is not a pathological condition, rather, a prematurely activated uncontrolled micturition; pathogenesis being anatomical damage in a nonlinear feedback control system comprising cortical and peripheral (muscle/ligament) components. METHODS: We examined studies from basic science, anatomy, urodynamics, ultrasonic and video xrays, ligament repairs, from which we created a nonlinear binary model of bladder function. We applied a Chaos Theory feedback equation, Xnext = Xc(1 - X) to test our hypothesis against existing concepts and hypotheses for OAB pathogenesis. RESULTS: The bladder has ONLY two modes, EITHER closed OR open (micturition). Closure is reflexly controlled cortically and peripherally: muscles contracting against ligaments stretch the vagina to suppress afferent signals to micturate from urothelial stretch receptors. "OAB" can be caused by anatomical damage anywhere in the model, by childbirth or age-weakened ligaments, which can be repaired to cure all three OAB symptoms. Urodynamic "DO" graphs are interpreted anatomically and by the feedback equation. CONCLUSION: OAB is in crisis. Our thesis of OAB as an uncontrolled micturition from anatomical defects in the bladder control system provides fresh directions for further development of new treatments, nonsurgical and surgical, to help break the crisis and bring hope and cure to 600 million women sufferers.

BoNT/A in the Urinary Bladder-More to the Story than Silencing of Cholinergic Nerves.

Botulinum neurotoxin (BoNT/A) is an FDA and NICE approved second-line treatment for overactive bladder (OAB) in patients either not responsive or intolerant to anti-cholinergic drugs. BoNT/A acts to weaken muscle contraction by blocking release of the neurotransmitter acetyl choline (ACh) at neuromuscular junctions. However, this biological activity does not easily explain all the observed effects in clinical and non-clinical studies. There are also conflicting reports of expression of the BoNT/A protein receptor, SV2, and intracellular target protein, SNAP-25, in the urothelium and bladder. This review presents the current evidence of BoNT/A's effect on bladder sensation, potential mechanisms by which it might exert these effects and discusses recent advances in understanding the action of BoNT in bladder tissue.

Efficacy of Transcutaneous Electrical Nerve Stimulation in the Management of Neurogenic Overactive Bladder: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to investigate the therapeutic effect of transcutaneous electrical nerve stimulation on neurogenic overactive bladder that is refractory to pharmacotherapy. METHODS: This randomized trial recruited 83 participants with neurogenic overactive bladder that were nonresponsive to 3-mo first-line anticholinergic drug treatment. Participants were randomized into treatment and control groups. Transcutaneous electrical nerve stimulation current consisting of biphasic square wave with pulse durations of 150 µs and pulse frequency set at 20 Hz were applied to for 30 mins once a day for 90 days. Stimulation was provided over the lateral aspect of the sacrum bilaterally of the electrodes. Patients in the transcutaneous electrical nerve stimulation group stopped taking the anticholinergic drugs. The control group continued to receive anticholinergic drugs for 90 days. The participants' Overactive Bladder Symptom Score, the Medical Outcomes Study 36-Item Short-Form Health Survey scores, urodynamic values, and voiding diary data were assessed before and after the therapy. RESULTS: The transcutaneous electrical nerve stimulation treatment group had significantly decreased Overactive Bladder Symptom scores compared with the control group (P < 0.001); in addition, half of the Medical Outcomes Study 36-Item Short-Form Health Survey scores were significantly improved in the transcutaneous electrical nerve stimulation group (P < 0.05). The patients treated with transcutaneous electrical nerve stimulation improved significantly voiding diary parameters at P < 0.05. Similarly, urodynamic values at P < 0.05 favored the experimental group over the control group. CONCLUSIONS: Applying daily transcutaneous electrical nerve stimulation over the sacral region for 90 days to patient with neurogenic overactive bladder improved overactive bladder symptoms of patients whose response to anticholinergic drugs is far inferior. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the therapeutic effect of transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder (NOAB); (2) Demonstrate the effectiveness of reflex suppression of the bladder using the TENS applied over the sacral region as a stimulation location; and (3) Confirm the TENS method using biphasic square waves with pulse durations of 150 µs and pulse frequencies of 20 Hz as applied is shown to be superior to anticholinergic drugs in managing NOAB. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The inhibitory effect of trimetazidine on detrusor contractility - a potential repositioning of trimetazidine for the treatment of overactive bladder.

OBJECTIVES: This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action. METHODS: We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca2+ levels in fura-2-loaded A7r5 cells. KEY FINDINGS: TMZ (300 or 1000 µM) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10-1000 µM) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K+ channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 µM) reduced both the CaCl2-induced contraction of depolarized DSM strips under Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells. CONCLUSIONS: TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca2+ transients and K+ channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.

Machine Learning for Urodynamic Detection of Detrusor Overactivity.

OBJECTIVE: To develop a machine learning algorithm that identifies detrusor overactivity (DO) in Urodynamic Studies (UDS) in the spina bifida population. UDS plays a key role in assessment of neurogenic bladder in patients with spina bifida. Due to significant variability in individual interpretations of UDS data, there is a need to standardize UDS interpretation. MATERIALS AND METHODS: Patients who underwent UDS at a single pediatric urology clinic between May 2012 and September 2020 were included. UDS files were analyzed in both time and frequency domains, varying inclusion of vesical, abdominal, and detrusor pressure channels. A machine learning pipeline was constructed using data windowing, dimensionality reduction, and support vector machines. Models were designed to detect clinician identified detrusor overactivity. RESULTS: Data were extracted from 805 UDS testing files from 546 unique patients. The generated models achieved good performance metrics in detecting DO agreement with the clinician, in both time- and frequency-based approaches. Incorporation of multiple channels and data windowing improved performance. The time-based model with all 3 channels had the highest area under the curve (AUC) (91.9 ± 1.3%; sensitivity: 84.2 ± 3.8%; specificity: 86.4 ± 1.3%). The 3-channel frequency-based model had the highest specificity (AUC: 90.5 ± 1.9%; sensitivity: 68.3 ± 5.3%; specificity: 92.9 ± 1.1%). CONCLUSION: We developed a promising proof-of-concept machine learning pipeline that identifies DO in UDS. Machine-learning-based predictive modeling algorithms may be employed to standardize UDS interpretation and could potentially augment shared decision-making and improve patient care.

Uso do estudo urodinâmico por ginecologistas e urologistas no Brasil / Use of the urodynamic study by gynecologists and urologists in Brazil

Objetivo: O estudo urodinâmico (EUD) é um conjunto de exames que estuda o armazenamento e o esvaziamento da urina e é amplamente utilizado por ginecologistas e urologistas na abordagem da incontinência urinária (IU) feminina, apesar da discussão sobre suas indicações. Os objetivos do estudo foram verificar se a urodinâmica é utilizada rotineiramente na abordagem conservadora e cirúrgica da IU feminina, e quais outras indicações clínicas, comparando as respostas entre ginecologistas e urologistas brasileiros. Métodos: Trata-se de uma pesquisa de opinião por meio de um questionário semiestruturado, composto por perguntas sobre a prática clínica em IU, enviado por e-mail a ginecologistas e urologistas, e realizada entre agosto de 2020 e janeiro de 2021. As respostas foram comparadas por meio de análises estatísticas. Resultados: Dos 329 participantes, 238 (72,3%) eram ginecologistas e 91 (27,7%), urologistas. A maioria dos ginecologistas (73,5%) e urologistas (86,6%) não solicita EUD antes do tratamento conservador da IU, mas o EUD é indicado rotineiramente no pré-operatório de cirurgias anti-incontinência. A maioria dos participantes indica EUD na abordagem inicial da bexiga hiperativa (88,2% vs. 96,7%) e há maior chance de o urologista solicitar mais EUD nessa situação (OR = 3,9). Para a maioria dos participantes, é necessário solicitar a urocultura antes do EUD. Conclusão: A maioria dos ginecologistas e urologistas brasileiros não solicita o EUD antes do tratamento conservador da IU, de acordo com as diretrizes nacionais e internacionais, e muitas vezes solicita antes do tratamento cirúrgico da IU feminina. A indicação desse exame na abordagem inicial da bexiga hiperativa idiopática deve ser revisada pelos participantes.(AU)

Change in the central control of the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis.

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

Urinary urgency acts as a source of divided attention leading to changes in gait in older adults with overactive bladder.

AIMS: There is a well-recognised but unexplained association between lower urinary tract symptoms including urgency and urgency incontinence and falls in older people. It has been hypothesised that urinary urgency acts as a source of divided attention, leading to gait changes which increase falls risk. This study aimed to assess whether urinary urgency acts as a source of divided attention in older adults with overactive bladder (OAB). METHODS: 27 community-dwelling adults aged 65 years and over with a clinical diagnosis of OAB underwent 3-Dimensional Instrumented Gait Analysis under three conditions; bladder empty, when experiencing urgency, and when being distracted by the n-back test. Temporal-spatial gait and kinematic gait data were compared between each condition using repeated measures ANOVA. RESULTS: Gait velocity decreased from 1.1ms-1 in the bladder empty condition to 1.0ms-1 with urgency and 0.9ms-1 with distraction (p = 0.008 and p<0.001 respectively). Stride length also decreased, from 1.2m to 1.1m with urgency and 1.0m with distraction (p<0.001 for both). The presence of detrusor overactivity did not influence these results (p = 0.77). CONCLUSIONS: In older adults with OAB, urinary urgency induced similar changes in gait to those caused by a distracting task. These gait changes are associated with increased fall risk. This may be part of the explanation for the association between falls and lower urinary tract symptoms in older people. Future research should examine the effect of pharmacological treatment of OAB on gait and on the effect of dual-task training on gait when experiencing urgency.

Percutaneous tibial nerve stimulation versus sham efficacy in the treatment of refractory overactive bladder: outcomes following a shortened 6-week protocol, a prospective randomized controlled trial.

PURPOSE: It is a prospective randomized controlled trial comparing the efficacy of percutaneous tibial nerve stimulation versus sham for a shortened 6-week protocol of treatment in management of refractory OAB in non-neurogenic adult patients. METHODS: A total of 50 adults with refractory non-neurogenic overactive bladder symptoms were randomized 1:1 to 6 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy. Overactive bladder symptom score as well as 3-day voiding diaries were completed at baseline and at 7th week, 3rd and 6th month. RESULTS: The 7th week, 3rd and 6th month symptom score assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation patients achieved statistically significant improvement in bladder symptoms with 52% reporting moderately improved responses compared to non-response of sham patients from baseline (P = 0.001). Voiding diary parameters after 6 weeks of therapy showed that PTNS patients had statistically significant improvements in frequency, voided volume and urgency urinary incontinence episodes compared to sham. No serious device-related adverse events or malfunctions were reported. CONCLUSION: A shortened 6-week treatment protocol with PTNS appears to be successful and more effective than sham in the treatment of refractory OAB. PTNS therapy is safe and effective in treating OAB symptoms with 52% success rate following a shortened 6-week protocol. The duration of treatment with PTNS can be halved compared to the conventional 12 weeks, which would make it more acceptable and cost effective for patients.

Overactive bladder syndrome is associated with detrusor overactivity and abnormal voiding pattern in nulliparous women.

BACKGROUND: Pregnancy and childbirth are frequently associated with overactive bladder syndrome (OAB). However, the role of parous effects in OAB among nulliparous (NP) women remains controversial. METHODS: This study investigated abnormal voiding patterns and detrusor overactivity (DO) among NP women with OAB in comparison with parous women. From August 2011 to December 2018, 906 patients met the inclusion criteria for participation and were divided into three groups: 221 patients in the NP group, 571 patients in the normal spontaneous delivery (NSD) group, and 114 patients in the cesarean section (CS) group. Urodynamic study examinations were performed, and the presence of DO, abnormal voiding patterns, and maximum urethral closure pressure (MUCP) was recorded. Data were analyzed using analysis of variance, χ2 tests, and independent t tests. RESULTS: Compared with parous women in the NSD and CS groups, patients in the NP group had a significantly higher prevalence of abnormal voiding patterns, DO, and MUCP. Furthermore, abnormal voiding patterns were significantly associated with DO and MUCP, respectively, especially in the NP group. CONCLUSION: We hypothesized that hypertonicity or poor relaxation of the pelvic muscle in NP women may cause functional BOO, which is related to their OAB.

Correlations between bladder wall thickness and clinical manifestations in female patients with detrusor underactivity and detrusor overactivity-with-detrusor underactivity.

BACKGROUND: Among female patients with lower urinary tract symptoms, detrusor underactivity (DU), and detrusor overactivity-with-detrusor underactivity (DO-DU) are two common diagnoses. Here, we investigated the correlations between bladder wall thickness (BWT) and clinical manifestations of the two diagnoses. METHODS: From 2011 to 2016, female patients with DU or DO-DU, diagnosed at our institute, were recruited. We analyzed their urodynamic parameters and collected three questionnaires (IPSS, UDI-6, OABSS). Using transabdominal sonography, the BWT was recorded. DU was defined as follows: maximum free flow rate (Qmax) ≤ 15 cc/s; detrusor pressure at maximum flow (PdetQmax) ≤ 20 cmH2O; bladder capacity > 150 cc. DO-DU was defined as follows: Qmax ≤ 15 cc/s; PdetQmax ≤ 20 cmH2O; bladder capacity ≤ 150 cc. The BWTs of the two groups were compared using the Mann-Whitney U test; the correlations among the BWTs and the results of three questionnaires were analyzed using Spearman's rank correlation coefficient. RESULTS: Forty-eight female patients with DU and 13 with DO-DU were recruited. Demographic data revealed no differences between the two groups. The mean BWT of the DO-DU patients was significantly larger than that of the DU patients (4.11 vs 3.42 mm; p = 0.001). In the DO-DU group, a high correlation existed between the BWT and some of the UDI-6 items (urgency incontinence: r = 0.831, p = 0.006; incontinence related to activity: r = 0.884, p = 0.002; small amounts of leakage: r = 0.809, p = 0.008). The BWT of the DO-DU patients also exhibited a moderate correlation with the urgency incontinence from the OABSS questionnaire (r = 0.679; p = 0.044). No correlations existed between the BWT of the DU patients and any of the data from the three questionnaires. CONCLUSION: The BWT in the DO-DU patients was significantly thicker than that in the DU patients. The DO-DU patients with thicker bladder walls also had higher UDI-6 scores for both urgency and urgency incontinence.

Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.

Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.

Regional activity and functional connectivity in brain networks associated with urinary bladder filling in patients with tethered cord syndrome.

PURPOSE: Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging using analyses of regional activity and functional connectivity of brain networks. This study was designed to demonstrate functional network alterations in patients with detrusor overactivity. MATERIALS AND METHODS: In this study, we recruited 36 patients with tethered cord syndrome who had detrusor overactivity and 34 normal controls. We used regional homogeneity and seed-based functional connectivity computational methods to reveal resting-state brain activity features associated with patients. RESULTS: Compared with normal controls, patients with tethered cord syndrome showed regional abnormalities, mainly in the bilateral frontal cortex, anterior and midcingulate cortex, and temporal lobes. When these regions were defined as seeds, we demonstrated widespread modification in brain networks. The brain-bladder network was not positively connected with the cognitive control network. Both altered regional activity and changed functional connectivity were found in the brain-bladder network. CONCLUSION: Patients with NDO, activated areas in the frontal lobe and anterior cingulate gyrus decreased significantly and have fewer brain activation areas in the caudate nucleus and hypothalamus (limbic system). In functional connectivity work, we found a small positive correlation in different regions of frontal lobe. This study helped us better to understand the characteristics of neural network modifications in patients with tethered cord syndrome.

Voiding behavior in awake unrestrained untethered spontaneously hypertensive and Wistar control rats.

The spontaneously hypertensive rat (SHR), a genetic model of high blood pressure, has also been studied as a potential model of overactive bladder. In vivo studies have confirmed the presence of surrogate markers of overactive bladder, including detrusor overactivity, increased urinary frequency, decreased bladder capacity and voided volume (VV), and afferent hypersensitivity to bladder irritation. However, these observations were during awake cystometry using implanted bladder catheters tethered to an infusion pump and artificially filled. We conducted experiments in awake unrestrained untethered age-matched female SHRs and Wistar rats to quantify naïve consumption and voiding behavior and the effect of capsaicin desensitization on consumption and voiding behavior. Food and water consumption, body weight, voiding frequency, and VV were recorded. Rats were placed in metabolism cages for 24 h, up to twice a week, from 17 to 37 wk of age. Compared with Wistar rats, SHRs exhibited decrease in VV and did not exhibit diurnal variation in VV between light and dark periods, suggesting that SHRs may have bladder hypersensitivity. Furthermore, SHRs may also have smaller bladder capacities, as they consumed less water, voided less volume (regardless of light cycle), and had equal urinary frequencies compared with age-matched Wistar rats. We detected no change in SHR voiding behavior following capsaicin desensitization, which was in contrast to a prior awake in vivo cystometry study describing increased VV and micturition interval in SHRs and suggests that C-fiber activity may not contribute to bladder hypersensitivity in SHRs.NEW & NOTEWORTHY We characterized the long-term (20 wk) voiding, defecation, and consumption behavior of age-matched spontaneously hypertensive and Wistar rats without the influence of anesthesia or catheters. Spontaneously hypertensive rats exhibited bladder hypersensitiviy that persisted for the 20-wk duration and was unaffected by capsacin desensitization.

Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review.

BACKGROUND: The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown. SUMMARY: This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. Key Messages: BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.

Prevalence and urodynamic characteristics of detrusor overactivity with impaired contractility in the community-dwelling elderly with non-neurogenic lower urinary tract symptoms: Is it from a single or two independent bladder dysfunctions?

PURPOSE: To identify the prevalence of detrusor overactivity with impaired contractility (DOIC) in the community-dwelling elderly and explore whether it is from a single or two independent bladder dysfunctions. MATERIALS AND METHODS: Based on a 10-year urodynamic database of the SEOUL Study Group, elderly patients who met inclusion criteria were selected. Bladder sensation, capacity, and compliance were designated as evaluation elements for storage function, and free maximal flow rate (Qmax) and post void residual volume, detrusor pressure at maximal flow (PdetQmax), and bladder voiding efficiency for voiding function. RESULTS: The prevalence rate of DOIC was 18.8% and 5.5% among 2,571 men and 688 women, respectively, and increased significantly with age. In men, patients with DOIC showed no differences in storage parameters and significantly lower free Qmax and PdetQmax among voiding parameters, compared to those with detrusor overactivity (DO) only. Compared to men with detrusor underactivity (DU) only, those with DOIC had worse parameters in the majority of storage and voiding functions. In women, most of the storage and voiding functions were worse in patients with DOIC than in those with DO only. On the other hand, women with DU showed lower PdetQmax and worse voiding functions than those with DOIC, although some parameters did not reach statistical significance. CONCLUSIONS: It seems that DOIC is developed from a coincidental combination of two independent DO and DU in men. In contrast, DOIC is likely to be an intermediate step during the process of progression from DO to DU in women.