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BackgroundThe aims of this study was determine if stimulation of tibial nerve afferents could induce a prolonged modulation of the micturition reflex in the rats.MethodsFifteen female Sprague Dawley rats (250-350 g) were fully decorticated and paralysed for the study. Tibial nerve stimulation (TNS) was delivered by inserting two pairs of needle electrodes close to the nerves at the level of the medial malleolus. Constant flow cystometries (0.07 ml/min) at about 10 min interval were performed and the micturition threshold volume (MTV) was recorded and used as the dependent variable. After 4 – 5 stable control recordings, the tibial nerves of both sides were stimulated continuously for 5 min at 10 Hz, 3 times threshold for α-motor axons. Six times of same stimulation were applied repeatedly with an interval of 5 min between the stimulations. The mean MTV was compiled from several cystometries in each half hour before the TNS and during, after 6 periods TNS.ResultsDuring the experiment, all the animals survived in a good condition with reasonably stable micturition reflexes, a significant increase in MTV was revealed after TNS. The best effect (mean 178%) occurred during the first 30 min after 6 periods of stimulation. This clear threshold increase remained for at least 5 h.ConclusionsA prolonged increase in MTV was demonstrated by a short periods of TNS repeatedly. This post stimulation modulatory effects of micturition reflex would provide a theoretical explanation for the clinical beneficial effect of TNS in patients with overactive bladder (OAB).

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 6 Hz 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 2 T. When stimulated at 15 Hz, TNS did not significantly (P 0.05) change the BCs at 1 T and 2 T.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.

Urodynamic investigation in conscious rats is widely employed to explore functional bladder disorders of various etiologies and pathogeneses. Rats can be placed in restraining cages or wide cabinets where they are allowed to move freely during cystometry. However, the requirements of special devices hampered the application of urodynamic test in freely moving rats, and whether the restraint has any effects on urodynamic parameters in conscious rats remains obscure. In the present study, we described a novel approach for urodynamic investigation in both restrained and freely moving conscious rats. In addition, we for the first time systematically compared the urodynamic parameters of rats in the two conditions. With the current method, we successfully recorded stable and repeatable intravesical pressure traces and collected expected reliable data, which supported the idea that the restraint does not affect the activity of the micturition reflex in rats, provided sufficient and appropriate measures could be applied during cystometry. Fewer technique problems were encountered during urodynamic examination in restrained rats than in freely moving ones. Taken together, conscious cystometry in rats placed in restraining cages with proper managements is a reliable and practical approach for evaluating the detrusor activity and bladder function.

Purpose To test the hypothesis that naftopidil prolongs intercontraction intervals in rats undergoing chronic stress as observed in previous animal models, voiding behavior and bladder function were measured and analyzed. Methods Female Sprague-Dawley rats weighing 200–230 g were exposed to repeated variate stress (RVS) for 1 week, chronic variable mild stress for 2 weeks, or simple mild stress for 1 week. Voiding behavior was assessed in metabolic cages. Voiding frequency and urine output were measured, and changes of these values were compared for the different types of stress. Micturition reflex was analyzed using unconscious cystometry. Naftopidil was administered orally at 30 mg/kg/day for 2 weeks. Results Unexpectedly, no stress-exposed rats exhibited increased micturition frequency compared to the normal nonstressed control. However, intercontraction intervals were shortened with each type of stress in the unconscious condition, especially by RVS (P

AIMS The aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. METHODS Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1 mL/min) at about 10 min interval. The selected afferents were stimulated continuously for 5 min at maximal intensity. The same stimulation was repeated six times with a pause of 5 min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. RESULTS After six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4 h later (n = 10, P

This study tested the hypothesis that sacral neuromodulation, i.e., electrical stimulation of afferent axons in sacral spinal root, can block pudendal afferent inhibition of the micturition reflex. In α-chloralose-anesthetized cats, pudendal nerve stimulation (PNS) at 3–5 Hz was used to inhibit bladder reflex activity while the sacral S1 or S2 dorsal root was stimulated at 15–30 Hz to mimic sacral neuromodulation and to block the bladder inhibition induced by PNS. The intensity threshold (T) for PNS or S1/S2 dorsal root stimulation (DRS) to induce muscle twitch of anal sphincter or toe was determined. PNS at 1.5–2T intensity inhibited the micturition reflex by significantly ( P < 0.01) increasing bladder capacity to 150–170% of control capacity. S1 DRS alone at 1–1.5T intensity did not inhibit bladder activity but completely blocked PNS inhibition and restored bladder capacity to control level. At higher intensity (1.5–2T), S1 DRS alone inhibited the micturition reflex and significantly increased bladder capacity to 135.8 ± 6.6% of control capacity. However, the same higher intensity S1 DRS applied simultaneously with PNS, suppressed PNS inhibition and significantly ( P < 0.01) reduced bladder capacity to 126.8 ± 9.7% of control capacity. S2 DRS at both low (1T) and high (1.5–2T) intensity failed to significantly reduce PNS inhibition. PNS and S1 DRS did not change the amplitude and duration of micturition reflex contractions, but S2 DRS at 1.5–2T intensity doubled the duration of the contractions and increased bladder capacity. These results are important for understanding the mechanisms underlying sacral neuromodulation of nonobstructive urinary retention in Fowler’s syndrome.

INTRODUCTION Low intensity focused ultrasound has recently been identified as a novel method of stimulating targeted neurons. We hypothesized that ultrasound stimulation of the posterior tibial nerve would inhibit bladder contractions in an established rat model of rhythmic bladder contractions. METHODS Cyclical detrusor contractions were initiated by placing a transurethral catheter in female rats and infusing saline into the bladder. Transcutaneous ultrasound pulses were then delivered to the lower extremity of a rat (overlying the posterior tibial nerve) using a single element spherically focused 250 kHz transducer. Sixty-three cycles were repeated at 2 kHz for 300 ms at peak negative pressure of 900 kPa pulsed at 0.5 Hz. RESULTS We report successful suppression of bladder contractions using ultrasound stimulation in 10 animals. The average latency between the initiation of ultrasound and suppression of bladder contractions was 3 min 23 s (±51 s), the average time of contraction suppression was 13 min and 50 s (±2 min 25 s) and the average time from the end of ultrasound to return of contractions was 9 min 37 s (±2 min and 30 s). CONCLUSION In this work, we demonstrate the ability of targeted transcutaneous ultrasound to inhibit rhythmic bladder contractions in anesthetized rats. Due to its non-invasive nature and ease of application, we believe ultrasound mediated suppression of the micturition reflex is potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

The Nociceptin/Orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand Nociceptin/Orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry, and assessed functional effects of NOP and [micro] opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder sub-urothelium revealed a remarkable several-fold increase in Detrusor Overactivity (p

Antimuscarinic agents are currently the first-line therapy for overactive bladder (OAB). Many urologists believe the pharmacologic management of OAB is not altogether satisfactory. Pharmacologic research is trying to provide answers to the issues of efficacy, tolerability, and convenience of new drugs. This paper discusses the rationale underlying the development of new compounds, provides an update of progress in the search for new therapies for OAB, and tracks their translation into clinical practice. It offers an insight into the mechanism of action, efficacy, side-effects, and "market status" of several drug categories targeting the central nervous system (adrenoceptor modulators, serotonin/norepinephrine reuptake inhibitors, tachykinin modulators, opioids), neuromuscular blocking agents (botulinum toxin A), selective modulators of the afferent branch of micturition reflex (vanilloid, nociceptin/orphanin FQ), autonomic nervous system modulators (β 3 -agonists), potassium and calcium channel openers, and nonsteroidal anti-inflammatory drugs.

Objective The study was designed to determine the effect of low frequency (2.5Hz) intraurethral electrical stimulation on bladder capacity and maximum voiding pressures. Materials and Methods The experiments were conducted in 15 virgin female Sprague-Dawley rats (220–250g). The animals were anesthetized by intraperitoneal injection of urethane (1.5g/kg). Animal care and experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Antwerp University (code: 2013-50). Unipolar square pulses of 0.06mA were used to stimulate urethra at frequency of 2.5Hz (0.2ms pulse width) in order to evaluate the ability of intraurethral stimulation to inhibit bladder contractions. Continuous stimulation and intermittent stimulation with 5sec ‘‘on’’ and 5sec ‘‘off’’ duty cycle were applied during repeated saline cystometrograms (CMGs). Maximum voiding pressures (MVP) and bladder capacity were investigated to determine the inhibitory effect on bladder contraction induced by intraurethral stimulation. Results The continuous stimulation and intermittent stimulation significantly (p

Prostaglandins (PGs) are well known as one of the chemical mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), PG synthesis inhibitors, are used for anti-nociception and/or anti-inflammation. We examine the effect of loxoprofen, an NSAID, on micturiton in acetic acid-induced bladder inflammation of the rats. In cystometrogram study with saline infusion into the urinary bladder, loxoprofen did not alter the interval of bladder contraction (IC, 107% of the control). IC was shortened by acetic acid infusion (65% of the control) and loxoprofen prolonged the IC (162% of acetic acid infused period). This prolonged IC was approximately same as the control. Loxoprofen did not alter the threshold pressure and the maximal voiding pressure. These data suggest that PGE2 might not play a part of normal micturition and may play a part of the micturition reflex during acetic acid infusion. That is, loxoprofen might be useful for pathological hyperreflex of the micturition.

To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L1 and L6 of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L1 but not at L6. These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.

Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of A bladd ...

The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder dome for saline infusion. A cuff electrode was placed around right tibial nerve for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2–4 times the threshold (T) intensity for inducing a toe movement was applied either during slow (0.08 mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no effect on the micturition reflex when it was applied during slow bladder infusion. However, the 30‐min TNS applied with an empty bladder induced poststimulation inhibition and significantly (P < 0.05) increased the bladder capacity to about 140% of prestimulation level in a 50‐min period following the termination of stimulation. The bladder compliance was also significantly (P < 0.05) increased after the 30‐min TNS. These results suggest that different mechanisms might exist in acute‐ and post‐TNS inhibition of micturition reflex. The animal model developed in this study will be very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function., This study suggests that different mechanisms might exist in acute‐ and poststimulation tibial inhibition of the micturition reflex. The animal model developed in this study is very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function.

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30–60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300–900 μg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes.

Background Traditional tibial nerve stimulation (TNS) has been used to treat overactive bladder syndrome (OAB), but there are some shortcomings. Thus, a novel alternative is needed for the treatment of OAB. The study investigated the effects of a new type of tibial nerve microstimulator on the micturition reflex in cats. Methods An implantable wireless driver microstimulator was implanted around the tibial nerve in 9 α-chloralose anesthetized cats. Cystometry was performed by infusing 0.9% normal saline (NS) or 0.25% acetic acid (AA) through a urethral catheter. Multiple cystometrograms were performed before, during, and after TNS to determine the inhibitory effect of the microstimulator on the micturition reflex. Results TNS at 2 threshold (T) intensity significantly increased the bladder capacity (BC) during NS infusion. Bladder overactivity was irritated by the intravesical infusion of 0.25% AA, which significantly reduced the BC compared with the NS infusion. TNS at 2 T intensity suppressed AA-induced bladder overactivity and significantly increased the BC compared with the AA control. Conclusion The implantable wireless driver tibial nerve microstimulator appears to be effective in inhibiting the micturition reflex during physiologic and pathologic conditions. The implantable wireless driver tibial nerve microstimulator could be used to treat OAB.

Spinal nerve (SN) stimulation inhibits the bladder rhythmic contraction (BRC) in anesthetized rats. This preparation was used to study the effects of electrical stimulation of the tibial nerve (TN) and the dorsal nerve of the clitoris (DNC) on BRC. Stimulation of the TN and DNC for 10 min produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. As observed with the SN, 10-Hz stimulation of either TN or DNC produced the greatest degree of inhibition, with lower or higher frequencies being either less efficacious or inactive. In contrast to the prolonged inhibition produced by SN stimulation, both TN and DNC stimulation produced “short” lasting inhibition of bladder contractions and the maximal inhibition occurred during stimulation. TN stimulation was effective over only a narrow range of current intensities [3–4 × motor threshold current for inducing a toe twitch ( Tmot)] and only at a frequency of 10 Hz. Stimulation of TN at 10 Hz, 3 × Tmot inhibited BRC to 23% of control. Ten-hertz DNC stimulation at 2 × TEAS, the threshold current for evoking a reflex anal sphincter contraction, decreased the frequency of contractions to 4% of control. Although compared with the respective threshold current the BRC response was more sensitive to DNC compared with TN stimulation, the absolute current required to reduce BRC using DNC stimulation appeared to be higher. Comparing the effects of TN and DNC stimulation to our previous results with SN stimulation, SN stimulation produces the largest duration and efficacy of bladder inhibition.

cycles recorded. We preformed S3 rhizotomies on two rabbits to evaluate potential interference of field stimulation. RESULTS: The control (4), rhizotomy (2) and stimulation (11) groups’ baseline CMGs were not significantly different from each other. No rabbit had unproductive contractions during baseline CMG. The control group’s amplitude, duration and intervals of all three micturition CMGs were within 20% of each rabbit’s baseline. There were no unproductive contractions in the control group. The two rabbits that underwent rhizotomy did not have a detrusor contraction after the dorsal roots were severed. The results for rabbits with stimulation could be divided into 3 groups based on their micturition pattern after stimulation. Two rabbits (Resilient Group) were relatively unchanged overall in their micturition cycles after stimulation with only new-onset of post-stimulation of unproductive contractions. Two rabbits (Overactive Group) exhibited an overactive voiding pattern with lower capacity (mean 27ml / 9ml), a shortened interval between contractions (0.16 / 0.13), shorter duration of contraction (0.56 / 0.43) and lower PVR. The majority (7) of the rabbits (Dysfunctional Group) exhibited a dysfunctional voiding pattern with larger capacity (17ml / 22ml), longer interval (2.27 / 2.01) and longer duration of contractions (1.63 / 0.53). CONCLUSIONS: Using electrical stimulation of rabbit pelvic floor muscles, we were able to describe both CMG and EMG changes in an animal model of pelvic floor overactive dysfunction. This model has potential for future pelvic floor applications.

The relation of olfaction to urination was studied in 14 dogs. A stimulating surface electrode was applied to the nasal mucosa and a recording electrode to each of the external (EUS) and internal (IUS

Urethrocystometry was performed during a provocative handwashing test in 163 patients, 115 of whom had a prior history of urge incontinence. Almost invariably, a rise in detrusor pressure, when present, followed a fall in urethral pressure, and both were preceded by urge symptoms. This pattern appears to conform to the concept of "urethral instability", "detrusor instability" and urge incontinence being different manifestations of a prematurely activated micturition reflex.

Aims The flow of fluid along the urethra is known to facilitate detrusor contraction during micturition. This reflex, previously described in awake ewes, helps to achieve complete bladder emptying. In anesthetized cats, another urethra to bladder reflex involving urethral cold receptors has been described. The aim of this study was to investigate whether the urethral reflex first described in awake ewes could also be temperature-dependent. Methods Experiments were performed on 10 healthy ewes. Urethral flows were performed by injecting 10 ml saline (ranging from 17 to 43°C) at the level of the proximal urethra. Catheterization of the bladder was performed so that detrusor pressure was continually recorded during the experiments. Results Urethral flows using body temperature saline (37–39°C) consistently evoked detrusor contraction. Urethral flows using saline at temperatures between 40 and 43°C induced detrusor contractions that were not significantly different from those observed at 37–39°C. Urethral flows using saline at temperatures below 37–39°C (17–36°C) resulted in a weaker or absent detrusor contraction. Conclusions In ewes, we have shown that urethral to bladder micturition reflex involving mechanoreceptors is decreased at temperatures below the physiological range. It is suggested that transient receptor potential vanilloid cation channels (e.g., TRPV4 which is activated by sheer/stress flows at near-body temperature) could be involved in this urethra to bladder reflex. In humans, this reflex has hardly been described and is still a matter of debate. Our results reinforce that its full investigation may require systematic use of a range of saline flows at different temperatures. Neurourol. Urodynam. 26:290–295, 2007. © 2006 Wiley-Liss, Inc.

Pharmacotherapy is the first-line treatment for overactive bladder, but many patients discontinue drug therapy because of intolerable side effects, expense, or lack of longterm adherence. Alternative treatments are needed for patients who are unable to tolerate pharmacotherapy or who do not derive the desired benefits. Sacral nerve stimulation therapy has evolved into one of the most widely accepted treatment modalities in the arena of neurourology. Sacral nerve stimulation activates or "resets" the somatic afferent inputs that play a pivotal role in the modulation of sensory processing for micturition reflex pathways in the spinal cord. This minimally invasive technology offers a safe, reliable, and durable treatment for lower urinary tract dysfunction.

Reflexes mediated by urethral sensory pathways are integral to urinary function. This study investigated the changes in bladder pressure and urethral sphincter activity resulting from electrical stimulation of afferents in the deep perineal nerve (DP), which innervates the urethra and surrounding muscles, before and after acute spinal cord transection (SCT) in cats anesthetized with α-chloralose monitored by blood pressure and heart rate. DP stimulation elicited bladder contractions before and after SCT but only if the bladder contained a sufficient volume of fluid (78% of the volume needed to cause distention-evoked reflex contractions). The volume dependency was mediated by a neuronal mechanism in the lumbosacral spinal cord and was not attributable to length-tension properties of the detrusor muscle. Stimulation at 2–40 Hz initiated bladder contractions, but 20–40 Hz was more effective than lower frequencies in evoking and sustaining bladder contractions for the duration of the stimulus train. Decreases in urethral sphincter activity occurred during sustained bladder contractions evoked by 20- to 40-Hz stimulation before and within 16 h after SCT. After SCT, average bladder pressure increases evoked by DP stimulation were smaller than those evoked before SCT, but in some animals, bladder pressures elicited by DP stimulation continued to increase as time after SCT increased and reached pretransection amplitudes at 8–16 h posttransection. These data confirm the presence of a spinal circuit that can mediate coordinated bladder–sphincter responses and show that afferents from the DP can activate this circuit under appropriate conditions.

Background: We examined the influence of rectal distention on the spinal micturition reflex and the mechanism underlying its inhibition of bladder contraction. Methods: Fourteen conscious female Sprague-Dawley rats were used in this study after transection of the lower thoracic cord. Isovolumetric cystometry was performed before and after distention of the rectum by inflation of a rectal balloon, followed by intrathecal injection of strychnine (a selective glycine receptor antagonist) or bicuculline (a GABAA receptor antagonist) into the lumbosacral cord. Results: Rectal distention (1.0–3.0 cm3) prolonged the interval, decreased the amplitude, and shortened the duration of bladder contraction, and eventually almost abolished bladder activity. After intrathecal injection of strychnine (0.001–10 µg) or bicuculline (0.001–1 µg) in animals with inhibition of bladder activity by rectal distention, the interval, amplitude, and duration of bladder contraction returned to baseline. Conclusion: These results suggest that there is an inhibitory rectovesical reflex in the lumbosacral cord of rats with spinal cord injury, which modulates the spinal micturition reflex via glycinergic or GABAergic mechanisms.

This unit describes a conscious rat model that allows the investigation of compounds administered by various routes (e.g., oral, intravenous and subcutaneous). This procedure can be used to examine the effects of agents on supraspinal, spinal and peripheral control of the micturition reflex, in addition to effects on parasympathetic neurotransmission and detrusor relaxation. One advantage to this procedure over anesthetized dog and rat models is the ability to determine pharmacological effects in the absence of possible interfering effects of anesthetics.

This study was undertaken to examine the change in intravesical saline volume during isovolumetric cystometry in the urethane anesthetized female rat. The ureters were transected bilaterally and their distal ends were ligated. To prevent leakage of intravesical fluid, the proximal urethra was ligated after inserting a urethral catheter into the bladder. In 13 rats in which the bladder was filled with different volumes of saline between 0.3 and 2.0 ml and maintained under isovolumetric conditions for 3 hours, intravesical volume decreased (4-79%) when initial intravesical saline volume was equal to or greater than 0.6 ml (n = 9). In 9 rats in which intravesical volume decreased, mean final volume was 0.68 +/- 0.09 ml. The percentage change in intravesical volume (y) significantly depended on initial volume (x) (y = -42x + 17, n = 13). In 7 rats in which the proximal urethra was ligated and the bladder was filled with different volumes of soybean oil between 0.25 and 2.0 ml, intravesical volume did not change. In 8 rats in which the bladder neck was ligated around a urethral catheter to block blood flow to the bladder and in which the bladder was filled with different volumes of saline (0.3-1.8 ml), intravesical volume decreased when initial volume was equal to or greater than 1.35 ml. These results demonstrate that intravesical saline is absorbed from the normal bladder wall when intravesical volume is greater than the volume (0.6 ml) necessary to evoke the micturition reflex in urethane anesthetized rats.

We studied the effect of MK-801, a potent non-competitive NMDA receptor antagonist, on the micturition reflex in anesthetized rats. Pretreatment with MK-801 (0.1-1 mg/kg i.v.) dose dependently increased the bladder capacity and reduced the micturition contraction. The ability of MK-801 to inhibit bladder voiding was confirmed in additional experiments in which the compound (30-50 micrograms/kg i.v.) transiently suppressed established bladder voiding produced by continuous bladder filling. MK-801 (1 microM) did not affect nerve-mediated contractions of the rat bladder or inhibit the response to capsaicin. These findings provide pharmacological evidence for an involvement of NMDA receptors in the micturition reflex pathways.

In our years of observation, confirmed over a large population of cows, suckling of the udder by the calf invariably leads to micturition in the cow, especially during the early postpartum period. We undertook a study to explain this suckling–micturition reflex. In our study, we monitored 30 cows for the suckling–micturition reflex without a local anesthesia to the udder, 10 cows with a local anesthesia to the udder, and 50 lactating women (after breastfeeding their infants) via a questionnaire. Our results showed that 27 of the 30 cows without local anesthesia urinated upon suckling, whereas the 10 cows under local anesthesia never urinated. Lactatingwomen never reported having a sensation to urinate during breastfeeding. It could not be a hormonal (oxytocin)-mediated response because the reflex is absent in humans. Because the reflex disappears in cows under local anesthesia to the udder, we attribute this to a nerve-mediated response. Hence, we propose that the anatomical location of the micturition center is in the lumbo-sacral segments (Swenson, 1984), and that lumbo-sacral nerve innervations of the udder of the