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

Abstract

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...

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