Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

Tai, Changfeng; Wang, Jicheng; Wang, Xianchun; Groat, William C. de; Roppolo, James R.

doi:10.1002/nau.20374

Cited by 88 publications

(108 citation statements)

References 32 publications

(58 reference statements)

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“…A previous study in intact cats with pudendal afferent stimulation found volume increases of 18% over no stimulation (61), and in chronic spinalized cats the increase in continent volume during pudendal nerve stimulation was 147% (53). Similar increases (22-366%) in continent bladder volumes result from genital afferent stimulation in the human (19,22,28,58,62).…”

Section: Discussionmentioning

confidence: 55%

Activation and inhibition of the micturition reflex by penile afferents in the cat

Woock

Yoo²,

Grill³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Woock JP, Yoo PB, Grill WM. Activation and inhibition of the micturition reflex by penile afferents in the cat. Am J Physiol Regul Integr Comp Physiol 294: R1880-R1889, 2008. First published April 23, 2008 doi:10.1152/ajpregu.00029.2008.-Coordination of the urinary bladder and the external urethral sphincter is controlled by descending projections from the pons and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in ␣-chloralose anesthetized male cats. Depending on the frequency of stimulation (range, 1-40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5-10 Hz inhibited distension-evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension-evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension-evoked contractions), stimulation at 20 -40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared with distension-evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal cord transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation. electrical stimulation; spinal cord injury; dorsal nerve of the penis; frequency dependence RECIPROCAL COORDINATION of the urinary bladder and the external urethral sphincter (EUS) to maintain continence and produce micturition is controlled by the pontine micturition center (2, 3, 24). The spinobulbospinal micturition reflex is also subject to modulation by peripheral afferent activity (29, 30) that can influence voiding efficiency (41). The objective of the present study was to quantify the effects of genital afferents traveling in the penile component of the somatic pudendal nerve on the micturition reflex in the cat.Activation of pudendal afferent nerve fibers can engage spinal (5) and spinobulbospinal (2, 3) reflexes that are integral to the regulation of bladder function. Fluid flow through the urethra activates pudendal afferents (56), and this flow-driven activation can elicit detrusor contractions and facilitate micturition (2, 44, 48). Furthermore, electrical stimulation of pudendal urethral afferents in the cat (5, 49) and human (21) elicits detrusor contraction, and these responses are preserved following decerebration and acute and chronic spinal cord transection (SCT;...

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Section: Discussionmentioning

confidence: 55%

Activation and inhibition of the micturition reflex by penile afferents in the cat

Woock

Yoo²,

Grill³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Afferent pudendal nerve electrical stimulation (PNS) has been demonstrated to inhibit the micturition reflex, abolish uninhibited bladder contractions and increase MCC in animals and humans with SCI. 5,6 These results indicate that PNS might be a promising treatment option for neurogenic bladder overactivity after SCI.…”

Section: Introductionmentioning

confidence: 80%

“…This approach has been introduced as another effective treatment option for suppressing involuntary detrusor contractions in patients with NDO. Previous PNS studies have indicated that electrical stimulation of the pudendal nerve can inhibit the NVC during bladder filling, suppress reflex voiding, and increase MCC in animals and humans with chronic SCI, 5,6 but there is no report regarding the inhibitory effect of PNS on bladder overactivity at the early stage of SCI. Our prior study shows that PNS can inhibit NVC during bladder filling in dogs with chronic SCI, but this can only increase MCC in the early period (1 month later).…”

Section: Discussionmentioning

confidence: 99%

Early low-frequency stimulation of the pudendal nerve can inhibit detrusor overactivity and delay progress of bladder fibrosis in dogs with spinal cord injuries

Liu

Chen

et al. 2013

Spinal Cord

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Objectives: To determine the inhibitory effects of pudendal nerve stimulation (5 Hz) on bladder overactivity at the early stage of spinal cord injury (SCI) in dogs, and to explore the possible effects on delayed progression of bladder fibrosis after SCI. Methods: The study was performed using six dogs with spinal cord transection at the T9-T10 level. Group 1 (three dogs) underwent low-frequency electrical stimulation of the pudendal nerve 1 day after spinal cord transection. Group 2 (three dogs) underwent only spinal cord transection. All dogs underwent urodynamic examination at 1 and 3 months after SCI. The bladders were removed for histological examination of fibrosis at 3 months after SCI. Results: Bladder capacity and compliance were significantly increased (Po0.05) by pudendal nerve stimulation in group 1 when compared with group 2 at 1 and 3 months after SCI. Non-voiding contractions (NVCs) were inhibited in group 1 compared with group 2. Collagen fibers were significantly increased and elastic fibers were significantly decreased (Po0.05) in group 2 when compared with group 1. Conclusion: Early low-frequency pudendal nerve stimulation can inhibit detrusor overactivity (DO), increase bladder capacity and delay the progression of bladder fibrosis.

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“…Neural circuits in the periaqueductal gray (PAG) and pontine micturition center (PMC) are known to employ GABA (16) but are unlikely to be primarily responsible for pudendal stimulation-evoked reflex bladder inhibition, as bladder inhibition by pudendal afferent stimulation remains intact following chronic spinal cord injury (45,47). Any central GABAergic pathways that are involved would have also been antagonized after administration of intravenous picrotoxin.…”

Section: Gabaergic Mechanisms Are Necessary For Bladder Inhibition Bymentioning

confidence: 99%

“…Low-frequency (ϳ10 Hz) pudendal afferent stimulation inhibits bladder contractions, thereby promoting continence in preclinical animal studies (4,46,52). Inhibition of bladder contractions and increased bladder capacities elicited by low-frequency pudendal afferent stimulation can also be achieved after chronic spinal cord injury (43,47). However, the mechanisms of action of PN stimulation-mediated bladder inhibition are unclear, and such knowledge may improve patient selection and enable improvements in therapy.…”

mentioning

confidence: 99%

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

McGee

Danziger

Bamford

et al. 2014

American Journal of Physiology-Renal Physiology

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McGee MJ, Danziger ZC, Bamford JA, Grill WM. A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation. Am J Physiol Renal Physiol 307: F921-F930, 2014. First published August 20, 2014 doi:10.1152/ajprenal.00330.2014.-Electrical stimulation of pudendal afferents can inhibit bladder contractions and increase bladder capacity. Recent results suggest that stimulation-evoked bladder inhibition is mediated by a mechanism other than activation of sympathetic bladder efferents in the hypogastric nerve, generating ␣-adrenergic receptor-mediated inhibition at the vesical ganglia and/or ␤-adrenergic receptor-mediated direct inhibition of the detrusor muscle. We investigated several inhibitory neurotransmitters that may instead be necessary for stimulation-evoked inhibition and found that intravenous picrotoxin, a noncompetitive GABAA antagonist, significantly and reversibly blocked pudendal afferent stimulation-evoked inhibition of bladder contractions in a dose-dependent manner. Similarly, intravenous picrotoxin also blocked pudendal afferent stimulation-evoked inhibition of nociceptive bladder contractions evoked by acetic acid infusion. Furthermore, intrathecal administration of picrotoxin at the lumbosacral spinal cord also blocked bladder inhibition by pudendal afferent stimulation. On the other hand, glycinergic, adrenergic, or opioidergic mechanisms were not necessary for bladder inhibition evoked by pudendal afferent stimulation. These results identify a lumbosacral spinal GABAergic mechanism of bladder inhibition evoked by pudendal afferent stimulation. electrical stimulation; bladder inhibition; pudendal nerve; dorsal nerve of the penis; GABA; picrotoxin IMPROVED BLADDER CONTROL IS an unmet need in persons with urinary incontinence (1) and in persons with neurological disease or injury, such as spinal cord injury (9). Electrical stimulation is a promising approach to treat overactive bladder (OAB), which can produce urgency and incontinence and impair quality of life (8, 32). In particular, pudendal afferent stimulation inhibits distension-evoked bladder contractions and improves continence (51). We sought to identify the mechanism(s) of bladder inhibition by pudendal afferent stimulation.Pudendal nerve (PN) stimulation may be an alternative to sacral nerve stimulation to improve continence (33), and in patients who do not respond to sacral neuromodulation it may be a successful treatment option (29,34,41). Low-frequency (ϳ10 Hz) pudendal afferent stimulation inhibits bladder contractions, thereby promoting continence in preclinical animal studies (4, 46, 52). Inhibition of bladder contractions and increased bladder capacities elicited by low-frequency pudendal afferent stimulation can also be achieved after chronic spinal cord injury (43, 47). However, the mechanisms of action of PN stimulation-mediated bladder inhibition are unclear, and such knowledge may improve patient selection and enable improvements in therapy.Initial studies suggested that pudendal afferent stimu...

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Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

Abstract: This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.

Cited by 88 publications

References 32 publications

Activation and inhibition of the micturition reflex by penile afferents in the cat

Activation and inhibition of the micturition reflex by penile afferents in the cat

Early low-frequency stimulation of the pudendal nerve can inhibit detrusor overactivity and delay progress of bladder fibrosis in dogs with spinal cord injuries

A spinal GABAergic mechanism is necessary for bladder inhibition by pudendal afferent stimulation

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