Micturition Reflex Research Articles

Daily acute intermittent hypoxia therapy 1‐week after moderate contusion spinal cord injury improves lower urinary tract function in rats

There is an increasing interest in the use of non-invasive acute intermittent hypoxia (AIH) as a therapeutic intervention to improve respiratory and locomotor function in spinal cord injury (SCI). SCI, however, also significantly disrupts normal bladder function, leading to detrusor overactivity, decreased voiding efficiency, and increased residual volume. Ongoing studies in our laboratory investigating the effects of AIH exposure in rats as a strategy for improving lower urinary tract (LUT) function following mid-thoracic SCI indicate that a single bout of AIH decreases the incidence of non-voiding bladder contractions (NVCs) and increases voiding efficiency. In the current study, we begin to evaluate the potential for AIH to be used as a therapy for inducing long-lasting improvements in SCI-induced LUT dysfunction. To accomplish this, we examined the effects of daily AIH (dAIH) administered for 7 consecutive days on both spontaneous awake micturition patterns and reflex micturition event (rME) behaviors in adult female Sprague-Dawley rats with mid-thoracic moderate contusion (200 kdyn) SCI. For these experiments, dAIH composed of five alternating 3-min exposures of hypoxia (12% O2) and normoxia (21% O2) was initiated 1-week after SCI, with awake micturition patterns being evaluated by overnight metabolic chamber measurements weekly for 2-3-weeks before and 4 weeks after SCI and rME behaviors elicited by continuous infusion of saline (0.04-0.09 ml/min) into the bladder being evaluated by cystometry at 4-weeks after SCI; daily normoxia (dNx; 21% O2 episodes) served as a control. The impact of SCI on hindlimb motor and LUT function prior to initiating dAIH or dNx treatment was evaluated using BBB scores and manually expressed urine volumes during post-operative care, and these measurements revealed that deficits and initial stages of recovery were similar (as expected) in both treatment groups. Serial metabolic chamber measurements in both dAIH- and dNx-treated rats that exhibited functional voids at 1-week post-SCI demonstrated that most rats exhibited some degree of functional recovery of micturition pattern behaviors. Only dAIH-treated rats, however, exhibited a recovery of void frequency pattern (i.e., number of voids and inter-void interval)to pre-SCI levels albeit with slightly increased void volumes; dNx-treated rats also had increased void volumes. Intravesical bladder pressure (BP) measurements during terminal cystometry experiments in urethane-anesthetized (1.4 g/kg) rats revealed that dAIH-treated rats exhibited a decreased incidence of NVCs and that voiding contractions had increased delta BP (peak BP-minimum BP) and dynamic voiding efficiency (void volume/fill volume) compared to dNx-treated rats. Taken together, these findings suggest that dAIH treatment produces beneficial improvements in LUT function lasting at least two weeks that include more efficient voiding and decreased NVCs, and further support the use of dAIH therapy to treat SCI-induced LUT dysfunction.

PIEZO2, a mechanosensor in the urinary bladder

The functions of the lower urinary tract to store and eliminate urine are regulated by complex neural pathways that coordinate the activity of the smooth and striated muscles of the bladder, urethra, and urethral sphincters.1 Besides control by the central nervous system, micturition reflexes are triggered by bladder filling that stretches the bladder wall and by urine flow in the urethra that triggers a urethra-to-bladder reflex facilitating bladder contraction and emptying. Both the urothelium and the mechanically sensitive afferents from the dorsal root ganglia are involved in stretch and pressure detection.

High percentage of neurologic deficits in the electrophysiology study of the lower urinary tract in patients with detrusor underactivity and chronic urinary retention.

Both detrusor underactivity (DU) and bladder outlet obstruction are the common causes of chronic urinary retention. Some novel treatment approaches focus on modulating micturition reflex and external urethral sphincter (EUS) function. This study used electrophysiologic (EP) studies to investigate the micturition reflex and EUS conditions of chronic urinary retention patients. Sixty patients with urodynamic DU and chronic urinary retention were studied using (1) bulbocavernous reflex (BCR) by electric stimulation, (2) electromyography (EMG) of the EUS, and (3) nerve conduction velocity (NCV) studies of the pudendal nerve. The EP findings were analyzed in DU patients with different etiologies. The BCR was positive in 41.7% of patients. In EMG studies, denervation, reinnervation, and reduced recruitment of the EUS were observed in 21.7%, 71.7%, and 88.3% patients, respectively. Decreased amplitude of pudendal nerve conduction in NCV studies was noted in 73.3% of patients. Patients with sacral neuropathy had a lower BCR positive rate (p = 0.001), a nonsignificant but higher denervation rate (p = 0.059) in EMG studies, and a higher rate of decreased amplitude in NCV (p = 0.011) than those without sacral neuropathy. Excluding patients with sacral neuropathy or diabetes mellitus, a high percentage of neurologic deficits was still detected in EP studies. Chronic urinary retention patients with urodynamic DU not only have bladder dysfunction, but also potential neuropathy in the sacral reflexes, pudendal nerve, or urethral sphincter innervation. The neurologic deficits explored in EP studies may affect the decision-making around the therapy to restore the voiding function in DU.

Frequency-Dependent Effects on Bladder Reflex by Saphenous Nerve Stimulation and a Possible Action Mechanism of Tibial Nerve Stimulation in Cats.

PurposeThe present study determined the effects of saphenous nerve stimulation (SNS) at different stimulation frequencies on bladder reflex and explored a possible action mechanism of tibial nerve stimulation (TNS) on bladder activity in cats.MethodsTwo bipolar nerve cuff electrodes were implanted on the saphenous nerve and the contralateral tibial nerve in 13 cats, respectively. Multiple cystometrograms were obtained to determine the effects of single SNS at different frequencies and that of combined SNS and TNS on the micturition reflex by infusing normal saline.ResultsSNS at 1 Hz significantly reduced the bladder capacity (BC) to 59.8%±7.7% and 59.3%±5.8% of the control level at the intensity threshold (T) and 2T, respectively (P<0.05), while that at 20 Hz significantly increased the BC to 130.6%±4.2% of the control level at 6T (P<0.05). The TNS and SNS at 20 Hz did not significantly change the BCs at 1T (P>0.05), while combined stimulation at 1T significantly increased the BC to 122.7%±1.9% of the control level and induced an inhibitory effect which was similar to that TNS at 2T.ConclusionsThe current study revealed that SNS reduced and increased BC depending on different stimulation frequencies. The combined SNS and TNS maximized the clinical efficacy at a low intensity. Also, SNS may be a potential therapeutic mechanism of TNS.

Cell Deformation at the Air-Liquid Interface Evokes Intracellular Ca2+ Increase and ATP Release in Cultured Rat Urothelial Cells.

Urothelial cells have been implicated in bladder mechanosensory transduction, and thus, initiation of the micturition reflex. Cell deformation caused by tension forces at an air-liquid interface (ALI) can induce an increase in intracellular Ca2+ concentration ([Ca2+]i) and ATP release in some epithelial cells. In this study, we aimed to examine the cellular mechanisms underlying ALI-induced [Ca2+]i increase in cultured urothelial cells. The ALI was created by stopping the influx of the perfusion but maintaining efflux. The [Ca2+]i increase was measured using the Ca2+ imaging method. The ALI evoked a reversible [Ca2+]i increase and ATP release in urothelial cells, which was almost abolished by GdCl3. The specific antagonist of the transient receptor potential vanilloid (TRPV4) channel (HC0674) and the antagonist of the pannexin 1 channel (10panx) both diminished the [Ca2+]i increase. The blocker of Ca2+-ATPase pumps on the endoplasmic reticulum (thapsigargin), the IP3 receptor antagonist (Xest-C), and the ryanodine receptor antagonist (ryanodine) all attenuated the [Ca2+]i increase. Degrading extracellular ATP with apyrase or blocking ATP receptors (P2X or P2Y) with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) significantly attenuated the [Ca2+]i increase. Our results suggest that both Ca2+ influx via TRPV4 or pannexin 1 and Ca2+ release from intracellular Ca2+ stores via IP3 or ryanodine receptors contribute to the mechanical responses of urothelial cells. The release of ATP further enhances the [Ca2+]i increase by activating P2X and P2Y receptors via autocrine or paracrine mechanisms.

Spinal Dopaminergic Mechanisms Regulating the Micturition Reflex in Male Rats with Complete Spinal Cord Injury.

Traumatic spinal cord injury (SCI) often causes micturition dysfunction. We recently discovered a low level of spinally-derived dopamine (DA) that regulates recovered bladder and sphincter reflexes in SCI female rats. Considering substantial sexual dimorphic features in the lower urinary tract, it is unknown if the DA-ergic mechanisms act in the male. Histological analysis showed a similar distribution of tyrosine hydroxylase (TH)+ neurons in the lower cord of male rats and the number increased following thoracic SCI. Subsequently, focal electrical stimulation in slices obtained from L6/S1 spinal segments of SCI rats elicited detectable DA release with fast scan cyclic voltammetry. Using bladder cystometrogram and external urethral sphincter (EUS) electromyography in SCI male rats, intravenous (i.v.) administration of SCH 23390, a D1-like receptor (DR1) antagonist, induced significantly increased tonic EUS activity and a trend of increased residual volume, whereas activation of these receptors with SKF 38393 did not influence the reflex. Meanwhile, blocking spinal D2-like receptors (DR2) with remoxipride had no effect but stimulating these receptors with quinpirole elicited EUS bursting to increase voiding volume. Further, intrathecal delivery of SCH 23390 and quinpirole resulted in similar responses to those with i.v. delivery, respectively, which indicates the central action regardless of delivery route. In addition, metabolic cage assays showed that quinpirole increased the voiding frequency and total voiding volume in spontaneous micturition. Collectively, spinal DA-ergic machinery regulates recovered micturition reflex following SCI in male rats; spinal DR1 tonically suppress tonic EUS activity to enable voiding and activation of DR2 facilitates voiding.

Delivery of the 5-HT2A Receptor Agonist, DOI, Enhances Activity of the Sphincter Muscle during the Micturition Reflex in Rats after Spinal Cord Injury.

Simple SummarySpinal cord injury often disrupts connections between the brain and spinal cord leading to a plethora of health complications, including bladder dysfunction. Spinal cord injured patients are left with symptoms such as a leaky bladder (the inability to hold their urine), frequent urinary tract infections, and potential kidney failure. However, previous studies have shown that manipulation of serotoninergic receptors can improve urinary performance following spinal cord injury. In the current study, we sought to explore how stimulation of a specific serotonergic receptor subtype can significantly enhance bladder function in spinal cord injured rats. To do so, we utilized spinal cord injured female rats that underwent various bladder performance evaluations combined with pharmacological intervention of a specific serotonergic subtype. Additionally, the primary site of action was investigated to determine effects elicited during various administration routes (e.g., directly into the cord, into the femoral vein, or into the skin). Stimulation of this receptor subtype, regardless of delivery route, improved activity of the external urethral sphincter and detrusor-sphincter coordination in spinal cord injured rats. Collectively, the results of these experiments have the potential to provide vital guidance for the development of therapeutic strategies to alleviate urinary dysfunction following spinal cord injury.Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT2A) receptors affects recovered bladder function, but it remains unclear if this receptor regulates the activity of the external urethral sphincter (EUS) following SCI. To elucidate how central and peripheral serotonergic machinery acts on the lower urinary tract (LUT) system, we employed bladder cystometry and EUS electromyography recordings combined with intravenous or intrathecal pharmacological interventions of 5-HT2A receptors in female SCI rats. Three to four weeks after a T10 spinal transection, systemic and central blockage of 5-HT2A receptors with MDL only slightly influenced the micturition reflex. However, delivery of the 5-HT2A receptor agonist, DOI, increased EUS tonic activity and elicited bursting during voiding. Additionally, subcutaneous administration of DOI verified the enhancement of continence and voiding capability during spontaneous micturition in metabolic cage assays. Although spinal 5HT2A receptors may not be actively involved in the recovered micturition reflex, stimulating this receptor subtype enhances EUS function and the synergistic activity between the detrusor and sphincter to improve the micturition reflex in rats with SCI.

Potential role of ghrelin on the micturition reflex in rats.

IntroductionThe aim of this study was to investigate the effects of intravenous ghrelin administration on the micturition reflex in rats.Material and methodsContinuous cystometrograms were performed with female Sparague-Dawley rats under urethane anesthesia. Stable micturition cycles were established, and ghrelin was then administered intravenously to evaluate changes in bladder activity. In this experiment investigating the role of opioid systems, ghrelin was administered intravenously at the time of first observed bladder contraction after intravenous administration of naloxone methiodide, an opioid receptor antagonist.ResultsIntravenous administration of ghrelin increased intercontraction interval that was dose-dependent. These inhibitory effects returned to pre-controls level within 80 minutes of administration. Similarly, intravenous administration of ghrelin increased threshold pressure in a dose-dependent fashion. These inhibitory effects of ghrelin were antagonized by intravenous naloxone methiodide administration.ConclusionsThese results show that ghrelin inhibits the micturition reflex through an opioid-dependent mechanism in rats under urethane anesthesia.

Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6–S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.

Les réflexes urétraux : revue de la littérature

The urethrosphincter complex is involved not only in maintaining urinary continence, particularly during effort, but also for the achievement of a complete and effective micturition. Indeed, the urethra is not a simple passive channel for the evacuation of urine from the bladder to the urethral meatus, since its resistive capacities and its possibilities of modulation of the micturition reflex depend on its reflex role either as a sensory afferent or as a neuro-muscular effector. It also participates in many genito-sexual and ano-rectal réflexes. This review of the literature describes the various reflexes of the urethra as a sensory stimulus or a neuromuscular effector. All articles referenced in this review were obtained from articles indexed on Pubmed-Medline, using the keywords: "urethral reflexes; "reflex bladder"; "urination reflex"; "intravaginal; vaginal"; "anorectal; sphincter"; "Storage and voiding"; "reflexes sneezing"; "cough reflex". Other articles were selected through references of the articles issued from the first research. Only articles in English and French have been selected. The articles concerned animal and human experiments. Eight hundred and sixty-four referenced articles were founded and a total of 75articles were included, describing the various reflexes mediated by the urethra acting as a sensory afferent or mechanical effector. We differentiated the known data in humans and animals. The urethra is a complex anatomical structure ensuring, through numerous reflex mechanisms, urinary continence. Urethral resistances are modulated during efforts and depends on the bladder capacity and the intensity of the efforts. During micturition, the coordination between the bladder and the urethra is mediated by reflex pathways organized at the cerebral, spinal and lumbosacral levels. The modulation of the micturition in term of efficacy and velocity, is due in part, to the re-afferentation of the spinal reflex by continuous stimulus of the urethral canal. Many of these reflexes are imperfectly described. Finally, the urethra is implicated in reflex loops of anal continence and sexual functions.

Alterations in detrusor contractility in rat model of bladder cancer

Urinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.

Ophiocordyceps sinensis: a prominent source of bioactive components for alleviating overactive bladder

Ophiocordyceps sinensis is one of the most sought-after medicinal fungi used to treat various medical conditions such as respiratory diseases, liver and kidney dysfunctions. In China, it is widely used for alleviation of frequent urination where patients treated with O. sinensis have shown improvement in nocturia, which is the most common symptom of overactive bladder (OAB). Many studies have reported its anticancer, anti-inflammatory, anti-oxidative, hypoglycaemic and vasorelaxation properties. These properties are attributable to the presence of bioactive components such as polysaccharides, proteins and nucleosides. This mini-review highlights the medicinal potential of O. sinensis in alleviating OAB, which is a debilitating condition with a profound impact on the quality of life in a high proportion of older people. Four possible mechanisms of action of O. sinensis are suggested. Firstly, the relaxation of bladder smooth muscle through calcium dynamic, production of nitric acid (NO) and adenosine triphosphate (ATP). A second mechanism proposed is through the suppression of micturition reflex. The unequivocal properties of O. sinensis as anti-inflammatory and anti-oxidant, are two other plausible explanations, as both chronic inflammation and accumulation of oxidative stress molecules are associated with OAB exacerbation. With the recent success in cultivation of O. sinensis and the positive results from toxicity studies, a better understanding of its pharmacological actions can be further substantiated, including its use for relieving OAB.

PIEZO2 in sensory neurons and urothelial cells coordinates urination.

Henry Miller stated that “to relieve a full bladder is one of the great human joys”.Urination is critically important in health, and ailments of the lower urinary tract (LUT) cause extensive pathological burden. Nevertheless, we take urination for granted, and in-depth mechanistic insight is lacking. We have witnessed advances in understanding the central circuitry in the brain that facilitates urination1–3. Beyond central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow4. Surprisingly, the mechanotransduction molecules and the cell types that function as the primary stretch and pressure detectors in the urinary tract are mostly unknown. We find that the mechanosensitive ion channel PIEZO2 is expressed in lower urinary tract tissues, where it is required for low-threshold bladder stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Importantly, both humans and mice lacking functional PIEZO2 have impaired bladder control, and humans report deficient bladder-filling sensation. This study pinpoints PIEZO2 as a key mechanosensor in urinary function. These findings enable future work that will unlock how urothelial cells and sensory neurons interact to control urination.

Sexual dimorphism of detrusor function demonstrated by urodynamic studies in rhesus macaques

The lower urinary tract (LUT) and micturition reflexes are sexually dimorphic across mammals. Sex as a biological variable is also of critical importance for the development and translation of new medical treatments and therapeutics interventions affecting pelvic organs, including the LUT. However, studies of LUT function with comparisons between the sexes have remained sparse, especially for larger mammals. Detrusor function was investigated by filling cystometry and pressure flow studies in 16 male and 22 female rhesus macaques. By filling cystometry, male subjects exhibited a significantly larger bladder capacity and compliance compared to females. Pressure flow studies showed a significantly higher bladder pressure at voiding onset, peak pressure, and elevation in detrusor-activated bladder pressure from the end of bladder filling to peak pressure in the male subjects. The activation of reflex micturition, with associated detrusor contractions, resulted in voiding in a significantly larger proportion of female compared to male subjects. A higher urethral outlet resistance is suggested in the male subjects. We conclude that sexual dimorphism of detrusor function is prominent in rhesus macaques, shares many features with the human, and merits consideration in translational and pre-clinical research studies of micturition and LUT function in non-human primates.

Inhibitory effects of a minimally invasive implanted tibial nerve stimulation device on non-nociceptive bladder reflexes in cats.

The present study investigated the inhibitory effects of a novel minimally invasive implanted tibial nerve stimulation device on non-nociceptive bladder reflexes in cats. A wireless minimally invasive implanted nerve stimulator was implanted adjacent to the left tibial nerve in seven cats. Multiple cystometrograms (CMGs) were obtained to determine the inhibitory effects of tibial nerve stimulation (TNS) at different frequencies and intensities on the micturition reflex by infusing normal saline (NS). TNS at 6Hz did not significantly change the bladder capacity (BC) compared to the control level at the intensity threshold (T), while TNS significantly (P < 0.05) increased the BC to 158.89 ± 20.57% of the control level at 2T. When stimulated at 15Hz, TNS did not significantly (P > 0.05) change the BCs at 1T and 2T. The minimally invasive implanted TNS device was shown to be effective in inhibiting the micturition reflex under physiologic conditions. Further studies are warranted to determine the inhibitory effects of TNS on nociceptive bladder reflexes.

Brain hydrogen sulfide suppresses the micturition reflex via brain GABA receptors in rats

We recently reported that hydrogen sulfide (H2S) is a possible relaxation factor in the rat bladder. However, there is no available information about the roles of central H2S in the micturition reflex, so we investigated the effects of centrally administered GYY4137 (H2S donor) and AOAA (H2S synthesis inhibitor) on the micturition reflex in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats. Cystometry was performed before and after the administration of GYY4137 (3 or 10 nmol/rat, icv) or AOAA (30 or 100 μg/rat, icv). In some rats, SR95531 (GABAA receptor antagonist, 0.1 nmol/rat, icv) or SCH50911 (GABAB receptor antagonist, 0.1 nmol/rat, icv) was administered 30 min before GYY4137 administration (10 nmol/rat, icv). Centrally administered GYY4137 dose-dependently prolonged the intercontraction intervals (ICI) without altering maximum voiding pressure (MVP). On the other hand, centrally administered AOAA dose-dependently shortened ICI without altering MVP. The AOAA (30 μg/rat, icv)-induced ICI shortening was reversed in the central presence of GYY4137 (10 nmol/rat, icv). Centrally pretreated SR95531 or SCH50911 significantly attenuated the GYY4137 (10 nmol/rat, icv)-induced prolongation of ICI, respectively. These findings suggest that endogenous brain H2S can inhibit the rat micturition reflex via both GABAA and GABAB receptors in the brain.

IJU this issue

In this issue, a total of 14 articles including seven Original Articles, two Urological Notes, four Editorial Comments and one Letter to the Editor are published. Momota et al. (Aomori, Japan) showed an association between the Geriatric 8 score and treatment by disease stages in patients with prostate cancer. Okita et al. (Aomori, Japan) reported that frailty had a significant association with the type of urinary diversion, which should be considered for the selection of urinary diversion in muscle-invasive bladder cancer patients undergoing radical cystectomy. Izumi et al. (Tokyo, Japan) investigated the prognostic significance of contact with the renal sinus as a risk factor for metastasis in T1 clear cell renal cell carcinoma after surgery. Komyakov et al. (St. Petersburg, Russia) studied the long-term results of ureteral reconstruction with the appendix in patients with long ureteral strictures. Fukumoto et al. (Tokyo, Japan) reported that 2-octyl cyanoacrylate can be used safely for laparoscopic adrenalectomy with the transumbilical approach, and might be useful for reducing postoperative pain in patients aged <50 years. Hata et al. (Fukushima, Japan) suggested that differentiation into myofibroblasts induced by transforming growth factor-b1 and insulin-like growth factor-binding protein 3 actively occurs during the growth process of benign prostatic hyperplasia. Chiba et al. (Hokkaido, Japan) identified that in the rat prefrontal cortex, 5-hydroxytryptamine 2A receptors excite the micturition reflex, whereas 5-hydroxytryptamine 7 receptors inhibit this reflex. Although, unfortunately, there is only a little space to introduce all the articles, each article has interesting, valuable content. Please enjoy this issue by all means. None declared.

The Brain and the Bladder: Forebrain Control of Urinary (In)Continence.

Neural circuits extending from the cerebral cortex to the bladder maintain urinary continence and allow voiding when it is socially appropriate. Injuries to certain brain regions produce a specific disruption known as urge incontinence. This neurologic symptom is distinguished by bladder spasticity, with sudden urges to void and frequent inability to maintain continence. The precise localization of neural circuit disruptions responsible for urge incontinence remains poorly defined, partly because the brain regions, cell types, and circuit connections that normally maintain continence are unknown. Here, we review what is known about the micturition reflex circuit and about forebrain control of continence from experimental animal studies and human lesion data. Based on this information, we hypothesize that urge incontinence results from damage to a descending pathway that normally maintains urinary continence. This pathway begins with excitatory neurons in the prefrontal cortex and relays subcortically, through inhibitory neurons that may help suppress reflex micturition during sleep and until it is safe and socially appropriate to void. Identifying the specific cell types and circuit connections that constitute the continence-promoting pathway, from the forebrain to the brainstem, will help us better understand why some brain lesions and neurodegenerative diseases disrupt continence. This information is needed to pave the way toward better treatments for neurologic patients suffering from urge incontinence.

424 - Role of group I and III metabotropic glutamate receptors in the micturition reflex in rats

424 - Role of group I and III metabotropic glutamate receptors in the micturition reflex in rats

130 - Inhibitory effect of ghrelin on micturition reflex in urethane-anesthetized rats

130 - Inhibitory effect of ghrelin on micturition reflex in urethane-anesthetized rats