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Noradrenaline inhibits autonomous activity in the isolated guinea pig bladder.

OBJECTIVE: To investigate the actions of noradrenaline and the specific alpha-adrenergic agonists cirazoline (alpha1) and UK14304 (alpha2), and beta-receptor agonists formoterol (beta2) and BRL37344 (beta3) on the phasic activity induced by muscarinic stimulation on the isolated guinea pig bladder, as the physiological significance of this activity is unknown but it may underlie non-micturition contractions (NMCs, which can be inhibited by sympathetic nerve stimulation) and the generation of bladder sensations. MATERIALS AND METHODS: All experiments were conducted using whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra and suspended in a heated chamber containing oxygenated Tyrode's solution at 33-35 degrees C and the intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface. RESULTS: Exposure to noradrenaline reduced the amplitude and frequency of the phasic activity. When noradrenaline was washed off there was a transient increase in frequency. There was marked desensitization with repeated applications of noradrenaline. Applying the specific beta3-agonist BRL37344 reduced the amplitude of the phasic activity while formoterol, a specific beta2-agonist, had no effect. Cirazoline, a specific alpha1-agonist, reduced the amplitude of the responses and significantly reduced the frequency of the phasic activity. UK14304, a specific alpha2-agonist, had no effect. Stimulation of the hypogastric nerve to the guinea pig bladder generates contractions. Prolonged nerve stimulation at low frequency (6.5 Hz) generated phasic rises in intravesical pressure which were inhibited by noradrenaline. Using short (5 s) periods of stimulation noradrenaline inhibited nerve-mediated contractions at all frequencies but was more effective at <10 Hz. CONCLUSION: These experiments show that sympathomimetic stimulation in the isolated whole bladder results primarily in an inhibition of phasic activity, but also a stimulation. Two receptor subtypes appear to be involved in the inhibition, alpha1 and beta3, suggesting that there may be many sites of action. These results are discussed in terms of the possible physiological significance of phasic activity and the potential importance of its inhibition, in the context of the causes of pathological changes in the bladder, particularly those associated with bladder overactivity, and the pharmacological approach to the alleviation of clinical symptoms.

Action Potentials↗

Experimental models to study the physiology, pathophysiology, and pharmacology of the lower urinary tract.

The lower urinary tract is subject to a number of functional disorders, the most common of which, in humans, is bladder overactivity. To understand its pathophysiological basis, several in vitro and in vivo methodologies have been developed. In vitro tension recording from multicellular strips is in widespread use, and alternative experimental arrangements to a conventional organ bath are described, the relative merits are discussed, and the different experimentally derived variables are evaluated. Other methodologies, such as skinned fibres and whole bladder preparations, are also described. Electromyography in the isolated bladder is now feasible, and its potential uses discussed. The use of isolated smooth muscle cells is presented, especially with respect to the measurement of intracellular ion concentrations and electrophysiological parameters. The development of methods to prepare other cell types from the lower urinary tract is also introduced. A large-scale culture of urothelial and smooth muscle cells is possible, and their use as experimental tools, as well as a substrate for the development of surgical implants, is presented. Finally, different in vivo models of the lower urinary tract are presented, with reference to their investigation of clinical problems. These include models of bladder outflow obstruction, bladder ischaemia, bladder denervation, and congenital abnormalities and their influence on foetal development of the lower urinary tract.

Animals↗

The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract.

PURPOSE: We review the physiology of bladder cooling response in experimental animals and humans, and present its clinical usefulness. MATERIALS AND METHODS: We describe experimental studies of the bladder cooling response, and more recent clinical retrospective and prospective studies of the bladder cooling test in adults and children. RESULTS: Studies indicate the existence of a segmental spinal bladder cooling reflex that originates from specific cold receptors in the bladder and urethral walls supplied by unmyelinated C-afferents. The reflex is positive in neurologically normal infants and children until about age 4 years. It becomes negative with further maturation of the nervous system but may be unmasked by pathological processes that disturb the descending neuronal control of normal voiding. A positive test in a patient with an overactive bladder requires further neurourological evaluation. CONCLUSIONS: The bladder cooling response originates from cold receptors within the walls of the lower urinary tract. The cooling response represents a neonatal reflex that may be unmasked by central neuropathology, analogous to the appearance of the Basbinki sign in pyramidal tract lesions. The bladder cooling test is a simple and valuable tool to support the diagnosis of neurourological disorders.

Adult↗

Botulinum toxin treatment of urethral and bladder dysfunction.

Botulinum toxin (BTX) is the most lethal naturally occurring toxin known to mankind. Injection of BTX into the urethral sphincter or bladder is an effective treatment for lower urinary tract dysfunction. We reviewed the literature on the mechanisms of action and clinical efficacy of BTX treatment in urologic diseases, with a focus on lower urinary tract dysfunction. Injection of BTX is safe and effective in the treatment of detrusor-sphincter dyssynergia, non-neurogenic pelvic floor spasticity, and refractory overactive bladder. Urodynamic assessment after sphincter injection with BTX reveals a decrease of bladder voiding pressure, urethral pressure profile, and post-void residual urine. An increase of the functional bladder capacity and a decrease of the bladder voiding pressure can be seen after bladder injection with BTX. Clinical improvement was found in a moderate percentage of treated patients in most reported series and lasted for 3 to 14 months without significant adverse effects. In addition, BTX-A treatment inhibits afferent-nerve-mediated bladder contraction. This analgesic effect may expand the application of BTX in the localized genitourinary tract pain syndrome, such as interstitial cystitis and prostatodynia. In conclusion, application of BTX is a promising treatment for lower urinary tract dysfunction with profound basic and clinical implications.

Anti-Dyskinesia Agents↗

Etiology, pathogenesis, and diagnosis of interstitial cystitis.

Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause of IC is most likely multifactorial and includes genetic and environmental factors. Various pathophysiological changes in the bladder, pelvis, and peripheral and central nervous systems have been identified, and this has led to the emergence of biologically specific treatment modalities. Interstitial cystitis is being diagnosed with increasing frequency; however, current diagnostic criteria are non-uniform, and there is significant overlap between chronic pelvic pain syndromes in men and women, interstitial cystitis, recurrent "cystitis," and the overactive bladder syndrome. The diagnosis of interstitial cystitis can be made clinically and by cystoscopy and hydrodistension. The sensitivity and specificity of urinary markers and the potassium sensitivity test have not been prospectively studied.

Journal Article↗

Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study.

OBJECTIVES: To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily. PATIENTS AND METHODS: This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily. RESULTS: Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine. CONCLUSION: In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.

Adolescent↗

Five-year outcomes of the tension-free vaginal tape procedure for treatment of female stress urinary incontinence.

OBJECTIVES: We evaluated the long-term efficacy and safety of a tension-free vaginal tape (TVT) procedure for the treatment of female stress urinary incontinence (SUI) in a Korean population. METHODS: We included 134 patients (mean age, 52.3+/-9.3 yr) who underwent the TVT procedure for SUI in three institutions and followed for 5 yr (mean, 67.0 mo; range, 60-76 mo) postoperatively. We analysed voiding diaries and complete multichannel urodynamic studies preoperatively as well as cough stress tests, uroflowmetry, and questionnaires postoperatively. RESULTS: The overall 5-yr success rates (cure/improved) were 94.9% (76.9% and 18.0%, respectively), with an 86.6% patient satisfaction rate. Although the success rates between 1 and 5 yr were similar (97.7% vs. 94.9%), the cure rate decreased from 90.1% to 76.9% (p<0.001) at 5 yr. The 5-yr cure rate for mixed urinary incontinence (MUI) was 72.0%, which was not significantly different from pure SUI (78.0%, p>0.05). Maximal flow rate dropped from 25.9+/-10.3ml/s to 20.4+/-8.6ml/s at 1 mo postoperatively and recovered to 24.8+/-8.5ml/s at 5 yr. Complications included bladder perforation in 5 patients (3.7%), tape cutting or release in 11 (8.2%), and persistent suprapubic pain in 3 (2.2%). Urgency and urge incontinence improved in 46.7% and 48.0% of patients, respectively. CONCLUSIONS: TVT was an effective and safe procedure for SUI and MUI with high success rates in the long-term follow-up. It also improved concomitant overactive bladder symptoms and initially reduced postoperative urine flow, which recovered over time.

Adult↗

Actions of the new antimuscarinic compound Lu 25-109 on isolated human and pig detrusor.

The aim of this study was to evaluate the effects of a novel antimuscarinic agent, Lu 25-109, a partial M1 receptor agonist, and M2/M3 receptor antagonist in human and pig detrusor to establish its affinity for muscarinic receptors in human detrusor and parotid gland and to compare the results with those obtained with oxybutynin. Effects on the detrusor were determined as regards the ability to inhibit carbachol-induced contractions and contractions induced by electrical field stimulation (EFS). Radioligand binding studies were performed to assess the ability to displace quinuclidinyl benzilate (3H-QNB) from muscarinic receptors in the detrusor and parotid gland. Lu 25-109 produced a concentration-dependent rightward shift of the concentration-response curves for carbachol in both human and pig detrusor, the pK(b) values being 6.2+/-0.1 (n=6) and 5.8+/-0.3 (n=6). Corresponding values for oxybutynin were 7.9+/-0.1 (n=7) and 7.8+/-0.1 (n=6). Contractions induced by EFS in human detrusor were almost completely inhibited by 100 micromol/L Lu 25-109 (84+/-4%; n=4). In contrast, EFS-induced contractions in pig detrusor were less sensitive to Lu 25-109, resulting in a final inhibition of 32+/-6% (n=9) with the highest concentration used (100 micromol/L). This difference in effect between human and pig detrusor was not observed with oxybutynin. Radioligand binding experiments demonstrated a small difference in affinity for Lu 25-109 in the parotid gland compared with the bladder, the pKi values being 6.2+/-0.1 versus 6.5+/-0.1 (n=4). Corresponding values for oxybutynin were 8.5+/-0.1 versus 8.2+/-0.1 (n=4). The results show that Lu 25-109 competitively and effectively antagonizes carbachol-induced contractions and contractions induced by EFS in human detrusor muscle. Even if Lu 25-109 were less potent than oxybutynin, it has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans.

Adult↗

Cyclophosphamide induced cystitis alters neurotrophin and receptor tyrosine kinase expression in pelvic ganglia and bladder.

PURPOSE: We examined neurotrophin and receptor tyrosine kinase (Trk) expression in the bladder and major pelvic ganglia (MPG) after cyclophosphamide induced cystitis in rats. MATERIALS AND METHODS: The bladder and MPG were used in immunohistochemical studies, enzyme-linked immunoassays and Western blots for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), TrkA and TrkB. Bladder postganglionic MPG cells were labeled by tracing techniques. RESULTS: NGF and BDNF expression was decreased in the bladder of all rats after cystitis (p < or =0.001). NGF and BDNF expression was increased in the MPG in male rats with cystitis (p < or =0.01). Cells expressing TrkA and TrkB immunoreactivity (IR) increased 78% to 81% in the MPG in male rats with cystitis. TrkA-IR or TrkB-IR bladder postganglionic cells increased 50% to 74% with cystitis. Cystitis increased TrkA-IR 5 to 10-fold and TrkB-IR 10 to 12-fold in detrusor muscle. TrkA-IR and TrkB-IR were prominent in control urothelium but decreased with cystitis. After cystitis TrkB-IR nerve fibers and TrkA-IR cellular infiltrates were more apparent compared to controls. CONCLUSIONS: Cystitis decreases bladder NGF and BDNF expression, whereas MPG expression is increased. This change may reflect neurotrophin release at the bladder and retrograde transport to the MPG. TrkA-IR and TrkB-IR are increased in bladder postganglionic cells and bladders with cystitis. This increase may reflect a shift in Trk staining from urothelium to detrusor muscle and nerve fibers with cystitis. Neurotrophin/Trk interactions in the bladder and MPG may contribute to bladder overactivity with cystitis.

Animals↗

Female urinary incontinence rehabilitation.

Pelvic floor rehabilitation (PFR) is an important and recommended strategy for the treatment of many urogynecological disorders including urinary incontinence (UI). The recognised pioneer of PFR is the American gynecologist Arnold Kegel who, over 50 years ago, proposed pelvic floor muscle exercises (PFME) to prevent and/or treat female UI. Kegel's techniques were successfully used by others too, but as the years passed these techniques sank into unjustified oblivion. In the 1980s in Europe the medical world's interest in PFME techniques gained ground, contemporaneously with functional electrical stimulation (FES) and biofeedback (BFB). As a general rule, the least invasive and least dangerous procedure for the patient should be the first choice, and behavioural and rehabilitative techniques should be considered as the first line of therapy for UI. The behavioural approaches in women with UI and without cognitive deficits are tailored to the patient's underlying problem, such as bladder training or retraining (BR) for urge UI. BR has many variations but generally consists of education, scheduled voiding, and positive reinforcements. The rehabilitative approaches comprise BFB, FES, PFME, and vaginal cones (VC). BFB allows the subject to modify the unconscious physiological events, while FES is aimed at strengthening perineal awareness, increasing the tone and trophism of the pelvic floor, and inhibiting detrusor overactivity. PFME play an extremely important role in the conservative treatment of UI and overactive bladder, and many studies have demonstrated their effectiveness. Many authors have used the different methods for PFR in a heterogeneous manner: the best results were obtained when protocols requiring the contemporary use of 2 or more techniques were followed.

Biofeedback, Psychology↗

[Tuberculosis of the urinary bladder: diagnosis and treatment].

Tuberculosis of the urinary bladder (UB) is registered in 10-45.6% patients with urogenital tuberculosis. It is a severe incapacitating complication of kidney tuberculosis which significantly lowers quality of life. The results of the standard therapy of 76 patients with tuberculous cystitis are analysed. UB tuberculosis is diagnosed more often in women, outcomes of their treatment are worse. Twenty six patients with UB tuberculosis at the stage of overactive bladder received polychemotherapy and adjuvant trospium. After 3 months urination frequency decreased 4.3 times, on the average; UB volume increased 4.7 times, on the average. Complications were not registered.

Adolescent↗

The effect of botulinum-A toxin in incontinent children with therapy resistant overactive detrusor.

PURPOSE: We determined the effect of detrusor injection of botulinum-A toxin in a cohort of children with therapy resistant non-neurogenic detrusor overactivity. This prospective study included therapy resistant children with overactive bladder. MATERIAL AND METHODS: During the study period of 19 months 10 boys and 11 girls were included. All patients showed decreased bladder capacity for age, urge and urge incontinence. Main treatment duration before inclusion was 45 months. A dose of 100 U botulinum-A toxin (Botox) was injected in the detrusor. RESULTS: Side effects were evaluated in all 21 included patients. The side effects reported were 10-day temporary urinary retention in 1 girl and signs of vesicoureteral reflux with flank pain during voiding in 1 boy, which disappeared spontaneously after 2 weeks. No further examinations were done since the boy refused. Two girls experienced 1 episode each of symptomatic lower urinary tract infection. Eight girls and 7 boys with a minimum followup of 6 months represent the study group for long-term evaluation. In this study group after 1 injection 9 patients showed full response (no more urge and dry during the day) with a mean increase in bladder capacity from 167 to 271 ml (p <0.001). Three patients showed a partial response (50% decrease in urge and incontinence) and 3 remained unchanged. Eight of the 9 full responders were still cured after 12 months, while 1 of the initially successfully treated patients had relapse after 8 months. The 3 partial responders and the patient with relapse underwent a second injection with a full response in the former full responder and in 1 partial responder. CONCLUSIONS: Botulinum-A toxin injection in children with non-neurogenic overactive detrusor is an excellent treatment adjunct, leading to long-term results in 70% after 1 injection.

Adolescent↗

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis.

Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF(1) and CRF(2), was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly (P < or = 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly (P < or = 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF(2) receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF(2) receptor expression increased in whole bladder with CYP-treatment, whereas no CRF(1) receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF(2) IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF(1) IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis.

Animals↗

[Bladder and sphincter disorders in multiple sclerosis. Clinical, urodynamic and neurophysiological study of 225 cases].

Two hundred and twenty-five patients with multiple sclerosis and bladder dysfunction were evaluated. 72% had urinary incontinence, 46% dysuria and 24% urinary retention. Detrusor hyperreflexia was the most common finding on cystometry (70%) and 9% of patients had areflexia. Coaxial needle electromyography was performed on all patients and 82% had detrusor-sphincter dyssynergia. Cortical evoked potentials following stimulation of the pudendal nerve were delayed in 72% and sacral evoked latency in 16% especially in patients with incontinence secondary to overactive bladder (25%), suggesting a conus medullaris lesion in these cases. Urologic complications were noted in 40%, with benign lesions in 24% (diverticula, urinary infections) and serious lesions in 16% (hydronephrosis, pyelonephritis, renal reflux). The most common treatment was anticholinergic drugs (efficacy in 92%), alphablockers agents (efficacy in 60%) and autocatheterism in 28%.

Adult↗

Electrical pelvic floor stimulation: a possible alternative treatment for reflex urinary incontinence in patients with spinal cord injury.

The present study demonstrates the clinical experience of pelvic floor stimulation using percutaneous implantable electrodes and implantable electrical stimulator for the treatment of reflex urinary incontinence in patients with spinal cord injury. Pelvic floor stimulation was carried out on six paraplegic patients who had urinary incontinence from an overactive bladder. After the percutaneous implantation of a pair of electrodes, chronic stimulation was carried out by employing an implanted receiver or an external pulse regulator. Within 4 to 16 weeks of electrical stimulation urinary incontinence was improved in four of the six patients. In two of these six patients, incontinence was completely abolished subjectively. Urodynamic investigations demonstrated an increased volume at the first unstable contraction (P < 0.01) in all of the patients. Inhibition of detrusor overactivity was obtained from this procedure. The stimulation effect appeared to be constant during chronic stimulation. This new procedure probably provides a stable and reliable stimulation effect for long term treatment, and may be an alternative treatment for previous external electrical pelvic floor stimulation.

Adult↗

Combined use of alpha-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction.

PURPOSE: We provide an overview of the medical literature supporting the combined use of muscarinic and alpha-adrenergic antagonist therapy for the treatment of voiding dysfunction. MATERIALS AND METHODS: The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. RESULTS: Although the mechanism of action of alpha-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. CONCLUSIONS: Based on the physiology of alpha-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome.

Adrenergic alpha-Antagonists↗

[Clinical Results of PNE Tests in 70 Patients with Different Bladder Dysfunctions].

PURPOSE: Prior to implantation of a sacral neuromodulator we carried out PNE tests (peripheral nerve evaluation test) with bilateral test stimulation to establish which patients might profit from this kind of therapy. In contrast to the original unilateral technique used by Tanagho and Schmidt, we performed bilateral PNE test stimulation. Moreover, we analysed the diagnostic characteristics of those patients who had positive PNE test results and could thus receive a chronic sacral neuromodulator. MATERIALS AND METHODS: We performed bilateral PNE test stimulation in 70 patients (mean age: 53.6 yrs; 41 with retention symptoms and 29 with a hyperactive detrusor) over a minimum of 3 days. Retrospectively, we analysed the distribution of diagnostic characteristics (retention vs. overactive bladder and neurogenic vs. idiopathic) in the implant recipients. RESULTS: All patients received bilateral PNE test stimulation, during which the stimulation amplitudes were adjusted individually for each side. 8 patients were treated with the original PNE-electrode (model 0 041 830 - 002, Medtronic Inc., USA) without success. Of the remaining 62 patients, who were treated with an improved electrode, the PNE test was successful in 32 cases (51.6 %). Twenty-seven of these patients suffered from a neurogenic bladder dysfunction, and, in 5 cases, the causes were idiopathic. CONCLUSIONS: Bilateral PNE-test stimulation and the use of advanced PNE electrodes (model 3057, Medtronic Inc., USA) led to a positive PNE result in 51.6 % of the tested patients. Of these, the group with neurogenic bladder dysfunctions showed the highest response rate. Compared with the success rates in the multicenter study, we were able to increase the overall PNE response rate significantly. For this reason, we prefer a bilateral PNE-test with side-specific stimulation.

Adult↗

Neurourology and pelvic floor dysfunction.

The levator ani muscles, endopelvic fascia, and muscular structures of the sphincter and the pelvic floor musculature (PFM) comprise one system. The physiological organization of Onuf's nuclei and of levator ani motorneurons as well as the reflex control of the tonic activity, that is essential for the generation of maintained force in slow-twitch muscle fibers, is an important part of the normal function of this system. In the human the motor cortex is crucial in voluntary motor control also of PFM, but other areas in the brain are involved in activities of the PFM related to emotional behavior e.g. micturition. Coordination between the urinary bladder, the urethra and the PFM is mediated by multiple reflex pathways organized in the brain and spinal cord. Some reflexes promote urine storage, whereas others facilitate voiding. It is also possible that individual reflexes might be linked together in a serial manner to create complex feedback mechanisms. The control of striated muscle in neurological lesions of the lower urinary tract is an active area of research and is producing results that are relevant to the problems of the neurogenic and idiopathic overactive bladder, whether these are caused by central nervous system or peripheral nerve lesions.

Brain↗