[Kidney transplantation in children with complex urogenital malformations-what should be considered?] / Kindernierentransplantation bei komplexen urogenitalen Fehlbildungen ­ was gibt es zu beachten?

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of end-stage renal disease (ESRD) in children. Approximately one third of children with CAKUT have lower urinary tract dysfunction (LUTD). AIM: This article highlights the important aspects that need to be considered in kidney transplantation of children with complex urogenital malformations. MATERIALS AND METHODS: The paper reviews the existing literature regarding the evaluation, preparation, perioperative management, and follow-up of children with complex urogenital malformations and ESRD undergoing renal transplantation. RESULTS: Comprehensive diagnostics are required before any pediatric kidney transplantation. If LUTD is suspected, voiding cystourethrography and a urodynamic examination should be performed. Treatment of symptomatic vesicoureterorenal reflux and LUTD is mandatory prior to pediatric kidney transplantation. Following successful kidney transplantation of children with congenital urogenital malformations, lifelong follow-up is required. Regular reevaluations of the bladder by means of urodynamic examinations are necessary. In patients following bladder augmentation with intestinal segments or urinary diversions in childhood, regular endoscopic examinations of the urinary tract are recommended to rule out secondary malignancy. CONCLUSION: Treatment of children with complex urogenital malformations should be carried out in centers with appropriate expertise.

Associations of Lower Extremity Muscle Strength, Area, and Specific Force With Lower Urinary Tract Symptoms in Older Men: The Baltimore Longitudinal Study of Aging.

BACKGROUND: Lower urinary tract symptoms (LUTS) in older men are associated with an increased risk of mobility limitations. Lower extremity muscle quality may represent a novel shared mechanism of both LUTS and mobility limitations. METHODS: We evaluated associations of thigh skeletal muscle measures (strength, area, and specific force) with total LUTS severity (American Urologic Association Symptom Index; AUASI) and voiding and storage subscores among 352 men aged ≥60 years enrolled in the Baltimore Longitudinal Study of Aging. Thigh muscle strength (Nm) was defined as maximum concentric 30°/s knee extensor torque, area (cm2), and specific force (Nm/cm2) defined as strength/area. Associations with AUASI score were estimated using multivariable linear regression and linear mixed models. RESULTS: Mean thigh muscle strength at baseline was 139.7Nm. In cross-sectional multivariable models, each 39Nm increment in thigh muscle strength and 0.28Nm/cm2 increment in specific force was associated with -1.17 point (95% CI: -1.93 to -.41) and -0.95 point (95% CI: -1.63 to -0.27) lower AUASI score, respectively. Similar associations were observed for voiding and storage subscores, although somewhat attenuated. In longitudinal analyses, baseline muscle measures were not associated with annual change in AUASI, and current changes in muscle measures and AUASI were unrelated. CONCLUSIONS: Cross-sectionally, higher thigh muscle strength and specific force were associated with decreased LUTS severity in older men. However, we did not observe concurrent worsening LUTS severity with declining thigh muscle strength, area, or specific force in longitudinal analyses.

The effect of botulinum toxin A in children with non-neurogenic therapy-refractory dysfunctional voiding - A systematic review.

INTRODUCTION: Dysfunctional voiding (DV) is a habitual voiding disorder caused by involuntary contraction or non-relaxation of the external urethral sphincter (EUS) during voiding. This contraction causes high post-void residuals (PVR), urinary incontinence and urinary tract infections (UTIs). Various treatments for DV are available, but some children do not respond. Intersphincteric botulinum toxin-A (BTX-A) may be a possible treatment for therapy-refractory children with DV. OBJECTIVE: The aim of this systematic review is to summarize the effects and safety of intersphincteric BTX-A as a treatment for therapy-refractory DV in children. METHODS: A systematic search in Embase, MEDLINE, Cochrane, and Web of Science databases was performed. Studies reporting on the usage of intersphincteric BTX-A as a treatment for DV in children were included. Data on PVR, maximum flow rate (Qmax), repeat injections and complications were extracted. RESULTS: From a total of 277 articles, five cohort studies were identified, reporting on 78 children with DV of whom 53 were female (68 %) and 25 were male (32 %). Sample sizes ranged from ten to twenty patients. Mean or median age at the time of intervention ranged from 8 to 10.5 years. Meta-analysis could not be performed due to lack of data. The narrative synthesis approach was therefore used to summarize the results. All studies showed significant decrease in PVR after BTX-A injection. Three studies showed a 33-69 % improvement on incontinence after BTX-A injection. Less UTIs were reported after treatment. A temporary increase in incontinence, UTIs and transitory numbness to the gluteus muscle were reported as side-effects. CONCLUSIONS: BTX-A could be a safe and effective treatment option for therapy-refractory DV in children by reducing PVR, UTIs and incontinence. Hereby, the synergistic effect of BTX-A and urotherapy should be emphasized in future management. Furthermore, this study identified gaps in current knowledge that are of interest for future research.

[Urine retention-From the symptom to the structure]. / Harnverhalt ­ vom Symptom zur Struktur.

Urinary retention describes the inability to urinate. Based on the symptoms and the amount of the initial residual urine formation, a differentiation can be made between acute and chronic forms. The cause can be a subvesical obstruction or a bladder atony. In addition to emergency treatment in the form of initial relief of the strain on the bladder by insertion of a catheter, the indication for a definitive treatment with a clarification of the question whether an acute or chronic event is present is also important. Although the selection of the catheter is subject to few criteria, the further structured approach is complex. Both decision trees are presented in this article.

Skeletal Muscle Health, Physical Performance, and Lower Urinary Tract Symptoms in Older Adults: the Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Lower urinary tract symptoms (LUTS) and mobility limitations are bidirectionally associated among older adults, but the role of skeletal muscle remains unknown. We evaluated cross-sectional associations of muscle health and physical performance with LUTS. METHODS: We used data from 377 women and 264 men age>70 years in the Study of Muscle, Mobility and Aging (SOMMA). LUTS and urinary bother were assessed using the LURN Symptom Index-10 (SI-10;higher=worse symptoms). Muscle mass and volume were assessed using D3-creatine dilution (D3Cr) and magnetic resonance imaging. Grip strength and peak leg power assessed upper/lower extremity physical performance. 400m walk, Short Physical Performance Battery (SPPB), and Four Square Step Test (FSST) assessed global physical performance. Mobility Assessment Tool-short form (MAT-sf) assessed self-reported mobility. We calculated Spearman correlation coefficients adjusted for age, BMI, multimorbidity, and polypharmacy, chi-square tests, and Fisher's Z-test to compare correlations. RESULTS: Among women, LURN SI-10 total scores were inversely correlated with FSST (rs=0.11,P=0.045), grip strength (rs=-0.15,P=0.006), and MAT-sf (rs=-0.18,P=0.001), but not other muscle and physical performance measures in multivariable models. LURN SI-10 was not associated with any of these measures among men. 44% of women in the lowest tertile of 400m walk speed versus 24% in the highest tertile reported they were at least "somewhat bothered" by urinary symptoms (P<0.001) whereas differences among men were not significant. CONCLUSIONS: Balance and grip strength were associated with LUTS severity in older women but not men. Associations with other muscle and physical performance measures varied by LUTS subtype but remained strongest among women.

A robotic approach to clamshell augmentation enterocystoplasty.

Augmentation cystoplasty (AC) is a well-established surgical option for the management of overactive bladder where conservative management has failed. We describe the case of a man in his 50s with chronic bladder dysfunction secondary to refractory detrusor overactivity and small capacity bladder. His lower urinary tract symptoms (LUTS) of urinary frequency and nocturia persisted despite pharmacological therapy and peripheral neural modulation; hence, he underwent surgical intervention for management of his bladder dysfunction. A robot-assisted clamshell enterocystoplasty was performed with a successful outcome. His LUTS have improved significantly post surgery. This case highlights modern advances in minimally invasive and robotic surgical techniques in the management of functional urological conditions. It also further demonstrates that the robotic approach is a viable option for AC, an operation traditionally performed as open surgery.

Bladder diary for illiterates: A novel method.

PURPOSE: Bladder diary is an integral part of urologic evaluation of lower urinary tract symptoms. One of its limitations is the requirement of a literate patient or attendant to complete it. We propose a novel method for recording bladder diary in illiterate individuals, with the aid of easily available materials from hospital, without any expenditure from the patients. METHODS: Forty-nine patients, who were required to fill the bladder diary as a part of their urological assessment, and were either illiterate or not literate enough to complete it themselves, were enrolled and admitted in the urology ward for 1 and a half days. Patients were provided with two 500 mL empty normal saline bottles for collection of each void, and a chart separately for day and night with diagrams of saline bottles to mark the corresponding level of urine. The amount of urine and frequency was also noted simultaneously by nursing staff each time for 24 h. The investigator interpreted the data marked on the charts by the patient and compared it with the data collected by the nursing officers. RESULTS: No statistically significant difference was found between the data collected by the nursing staff and patient data interpreted by the investigators, which included 24-h urine volume(p = 0.562), nocturnal output (p = 0.941), average voided volume (p = 0.709), maximum voided volume (p = 0.369), fluid intake (p = 0.401), frequency, nocturia and episodes of urgency and incontinence (p = 1). CONCLUSION: This method of recording bladder diary is a feasible, genuine, reliable and cost-free method which can be used in illiterates.

Diagnóstico y tratamiento de pacientes con vejiga neurogénica en la Unidad Técnica de Cirugía Pediátrica / Diagnosis and treatment of patients with Neurogenic bladder in the Surgery Technical Unit Pediatric

El presente trabajo toma como base el documento: "Manejo Urológico del Mielomeningocele" de las Guías de Atención Pediátrica, del Hospital De Pediatría "Juan P. Garrahan" de la ciudad de Buenos Aires - Argentina; de los autores: Dra. Carol Burek y Dra. Liliana Campmany. En la Unidad Técnica de Cirugía Pediátrica del Hospital de Especialidades Carlos Andrade Marín, se atienden por mes unos 50 a 70 pacientes afectos de vejiga neurogénica desde el nacimiento hasta la adolescencia. Es una enfermedad crónica que requiere un diagnóstico correcto con estudios de imagen y función de la vía urinaria además de un posterior manejo diario por parte de los padres con la guía del médico especialista.

This work is based on the document: "Urological Management of Myelomeningocele" from the Pediatric Care Guidelines of the Hospital De Pediatría "Juan P. Garrahan" of the city of Buenos Aires - Argentina; by the authors: Dr. Carol Burek and Dr. Liliana Campmany. In the Pediatric Surgery Technical Unit of the Carlos Andrade Marín Specialties Hospital, 50 to 70 patients affected by neurogenic bladder from birth to adolescence are treated every month. It is a chronic disease that requires a correct diagnosis with imaging and urinary tract function studies, as well as subsequent daily management by the parents under the guidance of the specialist.

Destroyed bladders: Characterization of progressive inflammatory cystitis.

PURPOSE: We identified a subset of patients with noninfectious cystitis who develop refractory symptoms marked by diffuse inflammatory changes, reduced bladder capacity, and vesicoureteral reflux (VUR), termed here as "progressive inflammatory cystitis" (PIC). Our objective was to describe the phenotype, disease outcomes, and pathologic findings of PIC. MATERIAL AND METHODS: A single institution retrospective cohort study of patients with PIC. Patients with a history of pelvic radiation, urologic malignancy, or neurogenic bladder were excluded. We describe cohort characteristics and use bivariate analyses to compare subgroups. Kaplan-Meier methods estimate time to urinary diversion. RESULTS: From 2008 to 2020, 46 patients with PIC were identified. The median age of symptom onset was 63 years old (interquartile range [IQR]: 56, 70) and the most common presenting symptoms were urinary urgency/frequency (54%) and incontinence (48%). Urodynamics showed a median maximum bladder capacity of 80 mL (IQR: 34, 152), commonly with VUR (68%) and hydronephrosis (59%). Ultimately 36 patients (78%) underwent urinary diversion at a median of 4.5 years (IQR: 2, 6.5) after symptom onset. Significant pathologic findings include presence of ulceration (52%), acute and chronic inflammation (68%), including eosinophils (80%), lymphoid follicles (56%), and mast cells in both lamina and muscularis propria (76%). CONCLUSIONS: PIC is a newly defined entity characterized by significantly diminished bladder capacity, upper tract changes, and relatively quick progression to urinary diversion. Larger prospective cohort studies are required to further characterize this severe phenotype of chronic noninfectious cystitis, aid earlier diagnosis, and guide management decisions.

The Innovative Approach in Functional Bladder Disorders: The Communication Between Bladder and Brain-Gut Axis.

Functional bladder disorders including overactive bladder and interstitial cystitis may induce problems in many other parts of our body such as brain and gut. In fact, diagnosis is often less accurate owing to their complex symptoms. To have correct diagnosis of these diseases, we need to understand the pathophysiology behind overlapped clinical presentation. First, we focused on reviewing literatures that have reported the link between bladder and brain, as the patients with bladder disorders frequently accompanied mood disorders such as depression and anxiety. Second, we reviewed literatures that have described the relationship between bladder and gut. There exist many evidences of patients who suffered from both bladder and intestinal diseases, such as irritable bowel syndrome and inflammatory bowel disease, at the same time. Furthermore, the interaction between brain and gut, well-known as brain-gut axis, might be a key factor that could change the activity of bladder and vice versa. For example, the affective disorders could alter the activity of efferent nerves or autonomic nervous system that modulate the gut itself and its microbiota, which might cause the destruction of homeostasis in bladder eventually. In this way, the communication between bladder and brain-gut axis might affect permeability, inflammation, as well as infectious etiology and dysbiosis in bladder diseases. In this review, we aimed to find an innovative insight of the pathophysiology in the functional bladder disorders, and we could provide a new understanding of the overlapped clinical presentation by elucidating the pathophysiology of functional bladder disorders.

Microbiome in urological diseases: Axis crosstalk and bladder disorders.

Since the identification of the human urinary microbiome, numerous studies have characterized this microbial community and improved our knowledge of its association with urinary diseases. This association between urinary diseases and microbiota is not confined to the urinary microbiota; it is interconnected with the microbiota of other organs. The gastrointestinal, vaginal, kidney, and bladder microbiota all affect urinary diseases because they work with their respective organs to control the growth and operation of the immune, metabolic, and nervous systems through dynamic bidirectional communication along the bladder-centered axis. Therefore, disturbances in the microbial communities may result in the emergence of urinary diseases. In this review, we describe the increasing and intriguing evidence of complicated and critical relationships that may contribute to the development and progression of urinary diseases through disruption of the microbiota in various organs.

[Urine retention-From the symptom to the structure]. / Harnverhalt ­ vom Symptom zur Struktur.

Urinary retention describes the inability to urinate. Based on the symptoms and the amount of the initial residual urine formation, a differentiation can be made between acute and chronic forms. The cause can be a subvesical obstruction or a bladder atony. In addition to emergency treatment in the form of initial relief of the strain on the bladder by insertion of a catheter, the indication for a definitive treatment with a clarification of the question whether an acute or chronic event is present is also important. Although the selection of the catheter is subject to few criteria, the further structured approach is complex. Both decision trees are presented in this article.

The accuracy of cystography under general anesthesia in children with vesicoureteral reflux.

PURPOSE: To examine the accuracy of cystography under general anesthesia in children with vesicoureteral reflux (VUR). MATERIALS AND METHODS: A prospective study of children who had VUR on cystography without general anesthesia (i.e., the gold-standard), and who are candidates for endoscopic VUR repair surgery. All children subsequently underwent a cystography under general anesthesia before injection using standardized method, which was compared to the gold-standard cystography. χ2 and Mann-Whitney U tests were used to compare proportions and medians between groups. RESULTS: Between 2017 and 2021, 126 renal units in 13 boys and 50 girls were included. Median age was 3.4 years (interquartile range [IQR] 1.5-6.5). Median time from cystography without to cystography with general anesthesia was 3.8 months (IQR 2.7-6). Of the 126 renal units, 96 had VUR on cystography without general anesthesia. On dichotomous analysis (no VUR vs. any VUR) sensitivity, specificity, negative and positive predictive values of cystography under general anesthesia were 47% (45/96), 87% (26/30), 34% (26/77) and 92% (45/49), respectively. Accuracy was 56.3%; Cohen's Kappa coefficient was 0.22, indicating poor agreement. In subgroup analysis, the sensitivity of cystography under general anesthesia was significantly lower in primary VUR (20% vs. 55% in secondary VUR, p = 0.01) and active VUR (14% vs. 52% in passive VUR, p = 0.008). CONCLUSION: Cystography under general anesthesia was poorly correlated to cystography performed while the child was awake or lightly sedated. Clinical decision relying on this cystography is questionable.

Disfunção vesical e intestinal na infância: abordagem multi-metodológica / Disfunción vésico-intestinal en la infancia: enfoque multimetodológico / Bladder and bowel dysfunction in childhood: multi-method approach

Resumo Objetivo Descrever o perfil sociodemográfico, o acesso e interesse em receber informações on-line sobre a disfunção vesical e intestinal, bem como compreender a vivência da família de crianças e adolescentes acometidos por essa disfunção. Métodos Trata-se de estudo multi-metodológico realizado em um ambulatório de Prática Avançada de Enfermagem em Uropediatria de um hospital de ensino da região centro-oeste do país. Resultados A vivência da família da criança com disfunção vesical e intestinal aponta para um impacto negativo no cotidiano podendo estar relacionado às condições sociodemográficas, a falta de conhecimento das famílias sobre os sintomas e aos estigmas associados à sua manifestação. Para tanto, o acesso a informações on-line apresenta-se como potencial ferramenta de apoio para melhorar a experiência da família da criança com os sintomas. Conclusão Os resultados expressam a caracterização sociodemográfica da criança e sua família e o acesso e interesse em receber informações pela internet sobre a disfunção vesical e intestinal, que podem ser importantes para a adesão e percepção de melhora nos sintomas refletindo na vivência familiar. Portanto, o enfermeiro que atua no contexto de cuidado em uropediatria precisa inovar em sua abordagem e implementar novas modalidades de assistência ou intervenções em saúde, principalmente por meio da incorporação de tecnologias baseadas na internet, visando à melhora da qualidade de vida tanto da família quanto da criança com disfunção vesical e intestinal.

Resumen Objetivo Describir el perfil sociodemográfico, el acceso y el interés en recibir información digital sobre la disfunción vésico-intestinal, así como comprender la vivencia de la familia de niños y adolescentes acometidos por esta disfunción. Métodos Se trata de un estudio multimetodológico realizado en consultorios externos de Práctica Avanzada de Enfermería en Urología Pediátrica de un hospital universitario de la región Centro-Oeste del país. Resultados La vivencia de la familia de niños con disfunción vésico-intestinal indica un impacto negativo en la cotidianidad, lo que puede estar relacionado con las condiciones sociodemográficas, la falta de conocimiento de las familias sobre los síntomas y los estigmas asociados a su manifestación. Para eso, el acceso a la información digital se presenta como una potencial herramienta de apoyo para mejorar la experiencia de la familia de niños con los síntomas. Conclusión Los resultados expresan la caracterización sociodemográfica de los niños y su familia y el acceso e interés en recibir información por internet sobre la disfunción vésico-intestinal, que puede ser importante para la adhesión y percepción de mejora de los síntomas y puede reflejarse en la vivencia familiar. Por lo tanto, los enfermeros que actúan en el contexto de cuidado en urología pediátrica necesitan innovar su enfoque e implementar nuevas modalidades de atención o intervenciones en salud, principalmente mediante la incorporación de tecnologías basadas en internet, con el objetivo de mejorar la calidad de vida tanto de la familia como de los niños con disfunción vésico-intestinal.

Abstract Objective To describe the sociodemographic profile, access and interest in receiving online information about bladder and bowel dysfunction as well as understand the experience of families of children and adolescents affected by this dysfunction. Methods This is a multi-methodological study carried out in an outpatient clinic of Advanced Nursing Practice in uropediatrics of a teaching hospital in midwestern Brazil. Results The experience of families of children with bladder and bowel dysfunction points to a negative impact on everyday life, which may be related to sociodemographic conditions, lack of knowledge of families about the symptoms and stigmas associated with its manifestation. To this end, access to online information is a potential support tool to improve the experience of children's families with the symptoms. Conclusion The results express children's sociodemographic characterization and their family and the access and interest in receiving information on the internet about bladder and bowel dysfunction, which may be important for compliance and perception of improvement in symptoms, reflecting on family experience. Therefore, nurses who work in the context of uropediatrics care need to innovate in their approach and implement new care modalities or health interventions, mainly through the incorporation of internet-based technologies, aimed at improving the quality of life of both the families and children with bladder and bowel dysfunction.

Reflections and perspectives on sacral neuromodulation in the treatment of refractory overactive bladder disorder / 国际外科学杂志

Overactive bladder (OAB) is a common urological condition. First-line treatment for OAB includes behavioral therapy as well as pharmacological treatment with M-blockers and β3-adrenoceptor agonists. Patients with OAB who fail behavioral therapy and do not achieve the desired outcome after 6-12 weeks of treatment with M receptor antagonists alone or who cannot tolerate the adverse effects of oral medications are referred to as refractory OAB. patients with refractory OAB can be treated with surgical interventions such as Sacral Neuromodulation (SNM), intravesical Botulinum Toxin type A. BTX-A and Percutaneous Tibial Nerve Stimulation. Compared with other procedures, SNM is highly effective and has a low incidence of adverse effects. The author contemplates that future studies of SNM for refractory OAB could be conducted to address the overall changes in intestinal flora-urinary flora-metabolomics and urinary control-related brain structure-spinal cord functional structure-peripheral pelvic floor nerve structure.

Emphysematous cystitis: two cases report / 中华泌尿外科杂志

The 2 patients were both aged females with medical history of diabetes mellitus. The chief complaints were both hyperpyrexia. Laboratory tests presented markedly elevated white blood cells and C-reactive protein, indicating severe systemic infections. Urine culture confirmed the growth of Escherichia coli. CT scan revealed thickened bladder wall with intraluminal and interstitial collections of gas. After the diagnosis of emphysema cystitis was established, conservative treatments including bladder drainage, strict glycemic control and sensitive antibiotics were administered timely. Both of the 2 patients got fully recovery after standard treatment.

Endoscopic management of a spontaneous rectus sheath hematoma causing bladder perforation.

Rarely pelvic hemorrhage events can lead to bladder perforation. We present a 48-year-old female who developed a spontaneous rectal sheath hematoma which perforated her bladder. Her case was monitored with serial MRI imaging and managed with two endoscopic clot resections which demonstrated new epithelialization of the bladder wall across the hematoma point of entry. We conclude that the bladder has an impressive potential to heal and select cases of symptomatic invasive bladder hematomas may be monitored with serial imaging and managed endoscopically.

Urinary Bladder Patch Made with Decellularized Vein Scaffold Seeded with Adipose-Derived Mesenchymal Stem Cells: Model in Rabbits.

BACKGROUND: To evaluate tissue regeneration of the urinary bladder after the implantation of a decellularized vein sown with autologous adipose-derived mesenchymal stem cells (ASC) on luminal surfaces. METHODS: New Zealand rabbits (n = 10) were distributed in two groups: Group Bioscaffold alone (G1)-decellularized vena cava (1 cm2) was implanted, and Group Bioscaffold plus ACSs (G2)-decellularized vena cava (1 cm2) containing ASCs were implanted. ASCs were expanded, characterized, and maintained for one week in culture with a decellularized vein scaffold. The implants were performed under general anesthesia using a continuous suture pattern. Afterward, 21 d (day) specimens were collected and analyzed by hematoxylin and eosin (HE) histology and scanning electron microscopy (SEM). RESULTS: The integrity of the urinary bladder was maintained in both groups. A superior regenerative process was observed in the G2 group, compared to the G1 group. We observed a greater urothelial epithelialization and maturity of the mucosa and submucosa fibroblasts. Furthermore, SEM demonstrated a notable amount of urothelial villus in the G2 group. CONCLUSION: Decellularized vena cava scaffolds were able to maintain the integrity of the urinary bladder in the proposed model. In addition, ASCs accelerated the regenerative process development, observed primarily by the new urothelial epithelization and the maturity of mucosa and submucosa fibroblasts.

Inhibitory effects of vibegron, a ß3-adrenoceptor agonist, on the myogenic contractile and mechanosensitive afferent activities in an obstructed rat bladder.

To determine the role of ß3-adrenoceptor agonists on bladder sensory facilitation related to bladder myogenic contractile activities in bladder hyperactivity, we investigated the effects of vibegron, a ß3-adrenoceptor agonist, on the bladder and sensory function by evaluating cystometry and mechanosensitive single-unit afferent activities (SAAs), respectively, in a male rat model of bladder outlet obstruction (BOO). BOO was created by partial ligation of the urethra. Ten days after the surgical procedure, cystometric and SAA measurements were taken under two distinct conditions: a conscious-restrained condition, in which the bladder was constantly filled with saline, and a urethane-anesthetized condition involving an isovolumetric process with saline. For each measurement, vibegron (3 mg/kg) or its vehicle was administered intravenously after the data were reproducibly stable. In addition, the expression of ß3-adrenoceptor and substance P (SP), a sensory neuropeptide, in the bladder was further evaluated following immunohistochemical procedures. Number of non-voiding contractions (NVCs) in cystometry was decreased after vibegron-administration, which was a significant change from vehicle group. Number of microcontractions and SAAs of Aδ- and C-fibers were significantly decreased by vibegron-administration. Furthermore, ß3-adrenocepor and SP were co-expressed in the suburothelium layer of the bladder. These findings indicated that vibegron showed inhibitory effects on NVCs and microcontractions of the bladder, and SAAs of the Aδ- and C-fibers in BOO rats. The study suggested that vibegron can partly inhibit the mechanosensitive afferent transduction via Aδ- and C-fibers by suppressing bladder myogenic contractile activities in the rat bladder hyperactivity associated with BOO.

The TRPM8 channel as a potential therapeutic target for bladder hypersensitive disorders.

In the lower urinary tract, transient receptor potential (TRP) channels are primarily involved in physiological function, especially in cellular sensors responding to chemical and physical stimuli. Among TRP channels, TRP melastatin 8 (TRPM8) channels, responding to cold temperature and/or chemical agents, such as menthol or icilin, are mainly expressed in the nerve endings of the primary afferent neurons and in the cell bodies of dorsal root ganglia innervating the urinary bladder (via Aδ- and C-fibers); this suggests that TRPM8 channels primarily contribute to bladder sensory (afferent) function. Storage symptoms of overactive bladder, benign prostatic hyperplasia, and interstitial cystitis are commonly related to sensory function (bladder hypersensitivity); thus, TRPM8 channels may also contribute to the pathophysiology of bladder hypersensitivity. Indeed, it has been reported in a pharmacological investigation using rodents that TRPM8 channels contribute to the pathophysiological bladder afferent hypersensitivity of mechanosensitive C-fibers. Similar findings have also been reported in humans. Therefore, a TRPM8 antagonist would be a promising therapeutic target for bladder hypersensitive disorders, including urinary urgency or nociceptive pain. In this review article, the functional role of the TRPM8 channel in the lower urinary tract and the potential of its antagonist for the treatment of bladder disorders was described.