Dynamic pelvic-pudendal reflex plasticity mediated by glutamate in anesthetized 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

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...

“…The solution of identical volume to tested agents was dispensed to serve as the vehicle. This selected dose of drug was used because previous studies showed that glutamate and NMDA could induce pelvic-pudendal reflex plasticity in urethane-anesthetized rats at this dose (44,45). Besides, previous studies showed that 5-HT 1A receptor antagonist may modulate micturition reflex at the spinal cord level (20,25,26).…”

Section: Methodsmentioning

confidence: 99%

“…Using in vivo animal preparations, we demonstrated that low-frequency repetitive stimulations (RS) on the pelvic afferent nerve elicited a form of activity-dependent reflex plasticity, spinal reflex potentiation (SRP) in the pelvic-urethra reflex activities (12,13,41,42,43,44,45). Such in vivo preparations used in these studies maintained the whole neural network within the the central nervous system intact, thus offering an animal model to explore the possibility that activity-dependent reflex plasticity can be regulated by a specific nucleus that projects nerve fibers to the site where plasticity occurs.…”

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confidence: 99%

Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats

Pan

Peng

Chen³

et al. 2008

This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 Ϯ 0.00 spikes/stimulation, n ϭ 40), whereas RS produced a long-lasting reflex potentiation (16.14 Ϯ 0.96 spikes/stimulation, n ϭ 40) that was abolished by D-2-amino-5-phosphonovaleric acid (1.60 Ϯ 0.89 spikes/ stimulation, n ϭ 40) and was attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (7.10 Ϯ 0.84 spikes/stimulation, n ϭ 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 Ϯ 2.23 and 28.29 Ϯ 2.36 spikes/stimulation, P Ͻ 0.01, n ϭ 10 and 20, respectively). Pretreatment of selective nicotinic receptor antagonist, chlorisondamine, reversed the facilitation on RS-induced reflex potentiation caused by nicotine (19.41 Ϯ 1.21 spikes/stimulation, P Ͻ 0.01, n ϭ 10) Intrathecal WAY-100635 and spinal transection at the T1 level both abolished the facilitation on reflex potentiation resulting from the DPT nicotine injection (12.86 Ϯ 3.13 and 15.57 Ϯ 1.72 spikes/stimulation, P Ͻ 0.01, n ϭ 10 each). Our findings suggest that activation of nAChR at DPT may modulate N-methyl-D-aspartic acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/ pathological relevance in the neural controls of urethral closure.acetylcholine; serotonin; WAY-100635; intrathecal; rats; N-methyl-D-aspartic acid; spinal reflex potentiation THE IMPORTANCE OF UNDERSTANDING the descending innervations coming from the brain stem to the spinal circuitry involved in the micturition function has been emphasized because it may offer the strategy for developing pharmacological therapy in micturition disorders (38). Researchers applied electric shocks to the pontine reticular formation to relate this site with micturition function and revealed that the pontine reticular formation plays an important role in descending control on the functions of the lower urinary tract (30,31,54,55,67). The cholinergic system in brain areas of the central nervous system regulates physiological functions, including micturition (18, 21, 40). Administration of cholinergic agonists to the pontine tegmentum affected urodynamic parameters in reflexive micturition cycles (31, 67). In addition, pharmacological blockage of the nicotinic cholinergic receptors (nAChR) in the pontine tegmentum using chlorisondamine, a nicotinic receptor antagonist, abolished the modulation exhibited by cholinergic agonists (40, 56), suggesting that...