Physiopathology of overactive bladder syndrome

The pathophysiology of OAB is complex, multifactorial and still largely unknown. Several pathophysiological mechanisms have been highlighted that may play a different role in different patient groups. There are now experimental evidences that support both the myogenic and neurogenic hypothesis, but in recent years the "integrative" hypothesis has been gaining more and more acceptance, where a disruption in the multiple interactions between different cell types (neurons, urothelium, interstitial cells, myocytes) and network functions represent a central element of lower urinary tract dysfunctions. Of utmost importance, a disorder in the urothelial sensory function and in the urothelial/suburothelial non-neural cholinergic system, favored by age and comorbidities, appears to be crucial for the development of the OAB. Neuroplastic and detrusor changes in OAB are broadly similar to those observed in bladders exposed to outlet obstruction, neuropathies, inflammation or aging, and may be driven by a common urothelial dysfunction. Several signaling substances and their receptors were found to be involved in central pathways of bidirectional communication between the different cell types in the bladder, and were shown to be modified in several animal models of OAB as well as in human models, indicating new potential therapeutic targets.     

Effects of overactive bladder syndrome on female sexual function

This study was to evaluate the impact of the symptoms of overactive bladder (OAB) syndrome on female sexual function. Seventy nine patients with OAB (OAB group) and 79 healthy women (control group) underwent physical examination at our center, and had their sexual function evaluated using the female sexual function index (FSFI). In accordance with the presence or absence of urge incontinence, the OAB group was further divided into the wet and dry groups. The sexual function was evaluated again after 3 months of pharmacotherapy. We investigate the difference of sexual function between OAB and control group. The effect of OAB severity and OAB pharmacotherapy on sexual function was also explored. There were no significant differences between OAB group and control group, including age, body mass index (BMI), education, occupation, fertility, parity, childbirth, and menopause. Compared with the control group, the OAB group had significantly lower FSFI scores. The respective mean ± standard error FSFI scores in the control group and the OAB group were 2.98 ± 1.07 and 2.27 ± 0.96 for desire, 3.48 ± 1.16 and 2.32 ± 1.44 for arousal, 4.60 ± 1.13 and 3.10 ± 1.95 for lubrication, 3.37 ± 0.87 and 2.63 ± 1.04 for orgasm, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual satisfaction, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual pain, and 22.24 ± 5.29 and 15.59 ± 7.47 for the total score (P < .05 for all comparisons). The scores for desire, lubrication, orgasm, sexual satisfaction, pain, and total FSFI between the OAB-dry and OAB-wet subgroup were similar while score of arousal in OAB-wet subgroup was significantly increased compared with that of OAB-dry. OABSS score was commonly used in the assessment of OAB severity. The difference of the FSFI scores among mild OAB group, moderate OAB group, and severe OAB group was statistically significant (P < .05). Female FSFI sexual function scores were significantly improved after OAB pharmacotherapy (P < .05). Women with OAB syndrome have poorer sexual function than healthy women. Patients with more serious OAB experience more disturbing sexual dysfunction. Female sexual function scores were significantly improved after OAB pharmacotherapy.     

Chronic pelvic pain syndrome and the overactive bladder: The inflammatory link

Although the causes of chronic prostatistis/chronic pelvic pain syndrome, painful bladder syndrome/interstitial cystitis, and overactive bladder remain unclear, inflammation may explain some of the causative and propagating features. Cytokines may play a role by recruiting inflammatory cells and ultimately in inducing symptoms. This paper reviews the role of cytokines in the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome, overactive bladder, and painful bladder syndrome/interstitial cystitis.     

Management of overactive bladder

Many people are affected by urinary urgency, which can be highly bothersome. Urgency is the cornerstone symptom of overactive bladder (OAB), commonly occurring in conjunction with urinary frequency and nocturia. Once other medical causes of similar symptoms have been excluded, first-line OAB management comprises fluid intake advice and bladder training, supplemented by antimuscarinic drugs if necessary. Urodynamic confirmation of the diagnosis is required for OAB patients whose symptoms are refractory to first-line interventions. If patients are severely bothered by OAB despite optimization of medical treatment, they may proceed to invasive treatments, including neuromodulation, enterocystoplasty, detrusor myectomy, or urinary diversion. Our burgeoning understanding of the complex cellular, neural and integrative physiology of the bladder offers new insights into the causative mechanisms of OAB, and reasons why patients sometimes fail to respond to treatment. Study of sensory information pathways in the lower urinary tract has led to identification of the urothelium, afferent nerves and interstitial cells as key cellular elements in OAB. In-depth knowledge of the hierarchy of central nervous system control is lacking, but functional imaging is beginning to elucidate the challenges that lie ahead. New treatments under investigation include botulinum neurotoxin-A injection, oral β(3)-adrenergic agonists, and novel modalities for nerve stimulation. The subjective nature of urinary urgency, the lack of animal models and the multifactorial pathophysiology of OAB present significant challenges to effective clinical management.     

The importance of bladder wall thickness in the assessment of overactive bladder

The assessment of bladder wall thickness using ultrasound has been postulated to contribute diagnostic information in patients with voiding dysfunction. In particular, several studies have focused on this tool’s role in patients with overactive bladder and detrusor overactivity. Given the evidence that increasing bladder outlet obstruction and detrusor overactivity cause detrusor hypertrophy, bladder wall thickness and its derivative, ultrasound-estimated bladder weight, may provide information regarding the severity of the underlying disease process. If proven as a diagnostic tool, this could provide clinicians with a test that is less invasive than urodynamics, the current gold standard. Unfortunately, enough discrepancy exists in the literature to prevent widespread application of this tool, and the role of bladder wall thickness assessment in the management of overactive bladder remains undetermined.     

琥珀酸索利那新治疗儿童膀胱过度活动症的研究概况

膀胱过度活动症(overactive bladder,OAB)是一种以尿频、尿急症状为特征的症候群,严重影响儿童的生活,琥珀酸索利那新为新一代毒蕈碱乙酰胆碱(M受体)拮抗剂,对于膀胱逼尿肌具有高选择性,可明显缓解儿童OAB症状,小剂量琥珀酸索利那新用于治疗儿童OAB是安全、有效的。该文就琥珀酸索利那新治疗儿童OAB的研究概况作一综述。     

Pharmacologic management of overactive bladder

Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.     

Surgical management for overactive bladder

The majority of patients with overactive bladder can be managed with office-based techniques. When medical therapy fails as treatment for overactive bladder, surgical intervention ranging from electrical stimulation administered in the office to extensive procedures, such as augmentation or urinary diversion, may be needed. Any surgical intervention should be tailored to the patient with consideration of the degree of his or her discomfort, underlying pathology, general health, and obviously the patient’s own motivation.     

Intravesical therapy for overactive bladder

Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic therapy. Despite the development of new antimuscarinic agents, many patients do not tolerate or fail to respond to oral therapy. Intravesical instillation therapy can provide an alternative method of managing bladder overactivity. Intravesical instillation of anticholinergics such as oxybutynin and atropine can achieve cholinergic blockade without producing systemic side effects. Botulinum A toxin injected directly into the detrusor has been shown in preliminary studies to increase bladder capacity and decrease uncontrolled bladder contractility for up to 6 months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers and when administered into the bladder, lead to an increase in functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect afferent innervation by blocking C-fiber afferents, leading to decreased bladder contractility and increased bladder capacity. Intravesical instillation therapy can provide an alternative treatment for the management of overactive bladder.     

Pathophysiology of refractory overactive bladder

Overactive bladder (OAB) is a common condition. The International Continence Society defines OAB as a symptom complex characterized by urgency with or without urge incontinence, usually with frequency and nocturia. The first‐line treatment for OAB includes behavioral therapy, such as caffeine reduction, fluid intake modification, weight reduction, bladder training, and pelvic floor muscle training, as well as treatment with antimuscarinic or β₃‐adrenoceptor agonist medications. However, less than half of all cases achieve satisfactory outcomes following first‐line treatment. Second‐line therapy considered if satisfactory responses are not achieved after 8 to 12 weeks treatment with first‐line therapy include intradetrusor botulinum toxin injection, neuromodulation, and surgical treatment. Patients with refractory OAB may have more severe symptoms or underlying pathophysiologies that were not resolved by the initial medication. The pathophysiologies of refractory OAB include occult neurogenic bladder, undetected bladder outlet obstruction, urethral‐related OAB, urothelial dysfunction with aging, chronic bladder ischemia, chronic bladder inflammation, central sensitization, and autonomic dysfunction. This article discusses the possible pathophysiologies of refractory OAB.     

Novel biomarkers for overactive bladder

Biomarkers constitute any objectively measurable indicator of a biological process. The classic biomarker used in the diagnosis of overactive bladder (OAB) has been detrusor overactivity, which is assessed urodynamically. In the search for a reliable, noninvasive alternative to urodynamics, interest has focused on genetic, imaging, and urinary factors. Along with other cytokines detectable in urine, prostaglandin E2 and nerve growth factor are indicators of low-grade inflammation. Although they correlate with OAB symptom severity, they have not been shown to have independent prognostic benefit. Imaging biomarkers have been investigated since the earliest days of video urodynamics. Despite extensive research on the ultrasonographic estimation of bladder wall thickness, further standardization of the technique is required before conclusions can be reached regarding diagnostic accuracy. Genetic factors contribute approximately half of the total risk for urgency incontinence. Functional polymorphisms of the cytochrome P450 IID6 gene significantly alter the metabolism of some commonly used anticholinergic drugs, but no genetic loci that influence risk of OAB have been definitively identified. The first genome-wide association studies for OAB are in progress, and should identify new susceptibility genes. Although current putative biomarkers correlate with OAB severity, much future work is required to assess their prognostic value, and establish their role in clinical practice.     

Passive transfer of Sjogren's syndrome IgG produces the pathophysiology of overactive bladder

OBJECTIVE: The presence, in patients with primary and secondary Sjogren's syndrome (SS), of autoantibodies that acutely inhibit M(3) muscarinic receptor (M3R)-mediated bladder contractions is difficult to reconcile with the fact that symptoms of detrusor overactivity and other features of cholinergic hyperresponsiveness occur in this disease. This study was undertaken to examine the in vivo effects of these autoantibodies on bladder function by examining bladder responsiveness and compliance following passive transfer of patient IgG to mice. METHODS: Contractile responses of isolated bladder strips both to the muscarinic agonist carbachol and to electrically evoked acetylcholine release were measured 48 hours after injection of mice with patient or control IgG. A whole bladder assay with intact neuronal pathways was developed to assess bladder wall compliance on filling cystometry. Expression of M3R in bladders from IgG-injected mice was assessed by immunohistochemistry. RESULTS: Passive transfer of SS IgG with inhibitory anti-M3R activity produced a paradoxical increase in contractile responses of detrusor strips to cholinergic stimulation. Cystometry of whole bladders revealed a corresponding decrease in bladder wall compliance and phasic detrusor contractions upon filling, replicating the urodynamic features of an overactive bladder. The features of cholinergic hyperresponsiveness were associated with increased postsynaptic M3R expression and were reproduced by injecting mice with a rabbit antibody against the second extracellular loop of M3R. CONCLUSION: These findings are consistent with the notion that there is initial inhibition of parasympathetic neurotransmission by antagonistic autoantibodies to M3R, which produces a compensatory increase in M3R expression in vivo. The enhanced cholinergic responses during bladder distention result in detrusor overactivity. We conclude that the overactive bladder associated with SS is an autoantibody-mediated disorder of the autonomic nervous system, which may be part of a wider spectrum of cholinergic hyperresponsiveness.     

Current management of refractory overactive bladder

Overactive bladder (OAB) is a common condition affecting one‐sixth to one‐fifth of the global population. The treatment of refractory OAB remains a challenge for urologists. Current treatment options include the use of combination therapy with antimuscarinic agents and beta‐3 adrenoceptor agonists, and treating underlying curable disorders. Intravesical botulinum toxin type A (BoNT‐A) injection, percutaneous tibial nerve stimulation, and sacral nerve stimulation are third‐line management therapies suggested by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (AUA/SUFU) guidelines. In rare cases, more invasive surgical interventions can be considered after explaining the benefits and risks to the patients. Augmentation cystoplasty has a high success rate; however, it has also been associated with a high complication rate. In contrast, detrusor myomectomy is an easy procedure, but the treatment outcome remains controversial. Liposome‐encapsulated BoNT‐A is administered via bladder instillation, and promising results have been obtained in preliminary studies. More therapies are currently being investigated, and transient receptor potential vanilloid 1 antagonists may be new type of medication. Radiofrequency ablation and other targets for neuromodulation have also been studied; however, more evidence is needed to confirm their efficacy.     

Botulinum toxin in the treatment of overactive bladder

Clinical effectiveness of botulinum toxin (BTX) in the treatment of both neurogenic and idiopathic detrusor overactivity has been demonstrated in several studies. However, different protocols and techniques have been used by authors. METHODS. Literature review on intradetrusor injection of BTX for detrusor overactivity. RESULTS. The greatest clinical experience reports the use of 200 and 300 U Botox?. Available data suggest that clinical efficacy, duration, and the side effect profile is similar at these doses. Very few data, on the other hand, are available regarding the clinical outcomes using the Dysport? preparation; isolated reports support that efficacy is similar when using a dosing range of 500 to 1000 SU with increased risk of systemic side effects using 1000 SU. A variety of injection volumes was used, demonstrating similar efficacy and tolerability profile. Clinical effect duration extends six to ten months in the majority of studies. Data suggest that a repeated injection scheme proves successful in the vast majority of initial responders. CONCLUSIONS. Safety, effectiveness, specificity and reversibility make BTX a new attractive treatment modality for overactive bladder syndrome. However, more experience is needed to standardize the injection protocol with respect to therapeutic outcomes and adverse effects.