Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms

Peters, Kenneth M.; Killinger, Kim A.; Boguslawski, Brian; Boura, Judith

doi:10.1002/nau.20823

Cited by 145 publications

(96 citation statements)

References 24 publications

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“…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).…”

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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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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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“…92 PNS may be an alternative neuromodulation therapy for refractory OAB, particularly in patients who do not respond well to SNS. [93][94][95] However, although a CE mark has been granted in Europe, PNS remains for investigational use only in the United States. Studies are ongoing to evaluate the effectiveness of PNS for bladder control following SCI and to study novel stimulation paradigms for more effective treatment of NLUTD.…”

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confidence: 99%

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

McGee

Amundsen²,

Grill³

2015

The Journal of Spinal Cord Medicine

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Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control.

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“…Instead, we would suggest that PNS is likely to be reserved for those whose symptoms are refractory to SNS. Such an approach has already been proposed for urinary tract dysfunction [42].…”

Section: Pudendal Nerve Stimulationmentioning

confidence: 99%

Advances in the Surgical Treatment of Faecal Incontinence

Thomas

Vaizey

2013

Curr Surg Rep

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Faecal incontinence is a common condition. Once conservative therapy has failed, surgical management of this problem is required. Over the last decade, neuromodulation has emerged as an effective and safe treatment. The most widely used form of neuromodulation is sacral nerve stimulation. The other less commonly used techniques are posterior tibial nerve stimulation and pudendal nerve stimulation. Anterior sphincteroplasty still has an important role to play in selected cases. If these treatments fail, then other therapies need to be considered. Recent advances in anal sphincter bulking agents and artificial sphincter devices offer some hope for these patients.

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Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms

Abstract: CPNS is a reasonable alternative in complex patients refractory to other therapies including sacral neuromodulation. Continued research is needed to fully assess long-term outcomes and identify predictors of success.

Cited by 145 publications

References 24 publications

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

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

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

Advances in the Surgical Treatment of Faecal Incontinence

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