Estrogen Modulates the Spinal N -Methyl- d -Aspartic Acid-Mediated Pelvic Nerve-to-Urethra Reflex Plasticity in Rats

Kamo I, Hashimoto T. Involvement of reflex urethral closure mechanisms in urethral resistance under momentary stress condition induced by electrical stimulation of rat abdomen. Am J Physiol Renal Physiol 293: F920-F926, 2007. First published July 11, 2007; doi:10.1152/ajprenal.00466.2006.-A novel method for evaluating the urethral resistance during abrupt elevation of abdominal pressure was developed in spinalized female rats under urethane anesthesia. Electrical stimulation of abdominal muscles for 1 s induced increases in both the intra-abdominal and the intravesical pressure in a stimulusdependent manner, and the bladder response was almost lost when the abdomen was opened. The lowest intravesical pressure during electrical stimulation that induced fluid leakage from the urethral orifice (leak point pressure) and the maximal intravesical pressure without urine leakage below the leak point pressure were evaluated as the indexes of urethral resistance. Lower urethral resistance was obtained in the rats whose pelvic nerves or somatic nerves containing pudendal nerves and nerves to iliococcygeus/pubococcygeus muscles were transected bilaterally. In contrast, transection of bilateral hypogastric nerves showed smaller effects. Duloxetine, a drug for stress urinary incontinence, enlarged the reflex urethral closing contractions that were induced by an increase in intravesical pressure and measured using a microtip transducer catheter in the middle urethra. This drug also increased the urethral resistance (leak point pressure), whereas it did not show any effect in the rats whose pelvic nerves were bilaterally transected, showing that the augmentation of the reflex urethral closure by the drug resulted in the elevation of the urethral resistance. From these findings, it was concluded that during momentary elevation of abdominal pressure, the reflex urethral closure mechanisms via bladder-spinal cord-urethral sphincter and pelvic floor muscles greatly contribute to the increase in the urethral resistance to prevent the urinary incontinence. stress urinary incontinence; leak point pressure; reflex urethral closing responses; duloxetine STRESS URINARY INCONTINENCE (SUI) is defined as the involuntary loss of urine during increments of abdominal pressure (stress condition) such as sneezing and coughing in the absence of bladder contractions (5,22). This disorder is very common in women over middle age and generally occurs as a result of defects in the various passive and reflex mechanisms that maintain urethral closure in the presence of elevated abdominal pressure (1, 4, 23). Recently, the nerve-mediated reflex urethral closure mechanisms have been considered to contribute to the urethral resistance during events causing elevation of intravesical pressure (P ves ) in rats (14). Electrophysiological studies also have provided evidence indicating functions of the glutamate-mediated bladder-to-urethra reflexes in rats (6,16,17). With the accumulation of findings of active urethral closure mechanisms, pharmacotherapy by dr...

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confidence: 99%

Involvement of reflex urethral closure mechanisms in urethral resistance under momentary stress condition induced by electrical stimulation of rat abdomen

Izumi¹,

Hashimoto²

2007

“…These impulses, therefore, induce EUS contraction to establish sufficient intravesical pressure for urine propulsion (11,29). Recent studies investigating SRP in pelvic nerve-to-EUS reflex activity have demonstrated that not only the pelvic nerve-to-EUS reflex activity itself but also the stimulationinduced SRP in such a reflex may play an important role in the urethra closure mechanism (31)(32)(33)(34)(35)(36). In the present study, superimposed pontine tegmentum stimulation produced facilitation in RS-induced SRP in pelvic nerve-to-EUS reflex activity, which suggests that descending modulation coming from the pontine tegmentum may also be essential for the physiological urethra closure functions.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, using in vivo animal preparations, we demonstrated that low-frequency repetitive stimulations (RS) on the pelvic afferent nerve might elicit a novel form of activitydependent reflex plasticity, i.e., a spinal reflex potentiation (SRP) in pelvic nerve-to-EUS reflex activity (9,10,(31)(32)(33)(34)(35)(36). Such an animal model is quite different from investigations using brain or spinal slices with a thickness of several millimeters and may maintain the whole neural network within the central nervous system as well as all the dorsal and ventral rootlets attached on the spinal cord intact, thereby offering a gateway to investigate modulations on the SRP resulting from a specific neuronal projection to the site where SRP occurs.…”

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confidence: 99%

Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats

Chen

Peng

Tung

et al. 2007

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This study was conducted to investigate whether dorsolateral pontine tegmentum stimulation modulates spinal reflex potentiation (SRP) and whether serotonergic neurotransmission is involved in such a modulation. Reflex activities of the external urethra sphincter (EUS) electromyogram in response to a test stimulation (TS; 1/30 Hz) or repetitive stimulation (RS; 1 Hz) on the pelvic afferent nerve in 35 anesthetized rats were recorded with/without synchronized train pontine stimulation (PS; 300 Hz, 30 ms) and/or intrathecal administrations of 10 l of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (NBQX;cyclohexanecarboxamide trihydrochloride (WAY 100635; 100 M), and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 100 M). The TS evoked a single action potential (1.00 Ϯ 0.00 spikes/stimulation), while the RS produced a long-lasting SRP (16.12 Ϯ 1.59 spikes/stimulation) that was abolished by APV (1.57 Ϯ 0.29 spikes/stimulation) and was attenuated by NBQX (7.42 Ϯ 0.57 spikes/stimulation). Synchronized train PS with RS (PSϩRS) produced facilitation in RS-induced SRP (25.17 Ϯ 2.21 spikes/stimulation). Intrathecal WAY 100635 abolished the facilitation in SRP as a result of the synchronized PS (14.66 Ϯ 1.58 spikes/stimulation). On the other hand, intrathecal 8-OH-DPAT elicited facilitation in the RS-induced SRP (25.16 Ϯ 1.05 spikes/ stimulation) without synchronized PS. Our findings suggest that dorsolateral pontine tegmentum may modulate N-methyl-D-aspartic acid-dependent SRP via descending serotonergic neurotransmission. This descending modulation may have physiological/pharmacological relevance in the neural controls of urethral closure. long term potentiation; SRP; pontine tegmentum; serotonin; WAY 100635; 8-OH-DPAT ACTIVITY-DEPENDENT REFLEX plasticity, known as long-term potentiation (4, 5, 42) and windup phenomenon (37,50,51,58), has been widely studied in the central neural system, including the hippocampus and the spinal cord, for exploring the mechanisms of memory (3, 41) and hypergesia (46, 57), respectively. Forms of activity-dependent reflex plasticity can be elicited by applying electric shocks (6, 13) and by reagent injections/perfusions to specific sites (24). On the other hand, an established/establishing reflex plasticity may be modified by genetic (50), pharmacological (23, 46), surgical (27, 48, 54), or behavioral manipulations (2, 47). To the best of our knowledge, few studies have explored the possibility of modulating activity-dependent reflex plasticity by activating the higher nucleus of a specific neural projection to the site, where the reflex plasticity occurs. However, modulating activity-dependent reflex plasticity from a neural nucleus may mimic the physiological conditions of neural functions and offer gateways to elucidate the physiological/pharmacological relevancies in such activity-dependent reflex plasticity (1).Kuru (29) emphasized the importance of understanding the descending innervations from the brain stem to modulate the spinal reflexes involved in pelvic viscera, incl...

“…Recent studies on pelvic-urethra reflex, using intact spinal cord preparations, have demonstrated a glutamatergic N-methyl-D-aspartate (NMDA)-dependent spinal reflex potentiation in which the activity of this reflex was dynamically potentiated by repetitive (29) and tetanic (30) afferent inputs. Because pathological potentiation in this reflex activity was suggested to underlie the hyperactive urethra (10, 11, 26 -28), the activity-dependent spinal reflex potentiation seems to be a novel animal model for studying urethra continent function (12,13,28,39,(41)(42)(43)(44).…”

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Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats

Chen

Huang

Kao

et al. 2008

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The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a glutamatergic ␣-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor antagonist, 100 M, 10 l) and D-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 M, 10 l]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 M, 10 l) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [␥-aminobutyric acid (GABA) A receptor antagonist, 100 M, 10 l] but not hydroxysaclofen (GABA B receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch. spinal cord; voiding dysfunction; glutamate; bicuculline; hydroxysaclofen THE MECHANISM INVOLVED IN micturition, which is the result of coordination between bladder detrusor and outlet, is intricate. Both elements, the detrusor and outlet, maintain a sound cycle of storage and evacuation that is controlled by a group of reflex and voluntary actions (54). During the storage phase of a micturition cycle, detrusor relaxes and urethra contracts to produce continence; while the detrusor contracts, with sphincter relaxes to void urine during the evacuation phase. Inhibition of external urethra sphincter (EUS) activity during evacuation is essential for sufficient bladder emptying (18, 49). The absence of suppression on EUS activity during voiding is one feature of the pathological condition referred to as detrusor-sphincter dyssynergia (51). Such a dyssynergic sphincter contraction results in high intravesical pressure and residual urine. Therefore, to achieve near-normal voiding function in patients with detrusor-sphincter dyssynergia, outlet resistance should be reduced.Arising from the puborectalis muscle, EUS innervated by the perineal branch of the pudendal nerve and external anal sphincter (EAS) innervated by the rectal branch of the pudendal nerve are both striated skeletal muscles that contract and relax voluntarily. A study investigating the coordination between the EUS and EAS muscles demonstrated these muscles shared in reflex actions as in dilatation a...