Superficial Peroneal Neuromodulation of Persistent Bladder Underactivity Induced by Prolonged Pudendal Afferent Nerve Stimulation in Cats

The purpose of this study is to determine if superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α‐chloralose anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8±10.9% of control and a significant reduction in bladder contraction amplitude to 56.0±5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5 to 2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine if the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4±10.7% and 132.4±14.2% of control, respectively, and increased contraction amplitude to 85.3±6.2% and 75.8±4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, while SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a non-invasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Bladder underactivity induced by prolonged pudendal afferent activity in cats

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly ( P < 0.05) increased bladder capacity while PNS at 4 T also significantly ( P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly ( P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly ( P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler’s syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler’s syndrome.

Development of stress-induced bladder insufficiency requires functional TRPV1 channels

Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We previously discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function, sensory nerve activity, and bladder wall remodeling were assessed in C57BL/6 and TRPV1 knockout mice exposed to intensified social stress using conscious cystometry, ex vivo afferent nerve recordings, and histology. Intensified social stress increased void volume, intermicturition interval, bladder volume, and bladder wall collagen content in C57BL/6 mice, indicative of bladder wall remodeling and underactive bladder. However, afferent nerve activity was unchanged and unaffected by the TRPV1 antagonist capsazepine. Interestingly, all indices of bladder function were unchanged in TRPV1 knockout mice in response to social stress, even though corticotrophin-releasing hormone expression in Barrington’s Nucleus still increased. These results suggest that TRPV1 channels in the periphery are a linchpin in the development of stress-induced bladder dysfunction, both with regard to increased sensory outflow that leads to overactive bladder and bladder wall decompensation that leads to underactive bladder. TRPV1 channels represent an intriguing target to prevent the development of stress-induced bladder dysfunction in children.

Saphenous nerve stimulation normalizes bladder underactivity induced by tibial nerve stimulation in cats

This study in α-chloralose-anesthetized cats aimed at investigating the bladder responses to saphenous nerve stimulation (SNS). A urethral catheter was used to infuse the bladder with saline and to record changes in bladder pressure. With the bladder fully distended, SNS at 1-Hz frequency and an intensity slightly below the threshold (T) for inducing an observable motor response of the hindlimb muscles induced large amplitude (40–150 cmH2O) bladder contractions. Application of SNS (1 Hz, 2–4T) during cystometrograms (CMGs), when the bladder was slowly (1–3 ml/min) infused with saline, significantly ( P < 0.05) increased the duration of the micturition contraction to >200% of the control without changing bladder capacity or contraction amplitude. Repeated application (1–8 times) of intense (4–8T intensity) 30-min tibial nerve stimulation (TNS) produced prolonged post-TNS inhibition that significantly ( P < 0.01) increased bladder capacity to 135.9 ± 7.6% and decreased the contraction amplitude to 44.1 ± 16.5% of the pre-TNS control level. During the period of post-TNS inhibition, SNS (1 Hz, 2–4T) applied during CMGs completely restored the bladder capacity and the contraction amplitude to the pre-TNS control level and almost doubled the duration of the micturition contraction. These results indicate that SNS at 1 Hz can facilitate the normal micturition reflex and normalize the reflex when it is suppressed during post-TNS inhibition. This study provides an opportunity to develop a novel neuromodulation therapy for underactive bladder using SNS.

Recent advances in pharmacological management of urinary incontinence

Lower urinary tract symptoms—in particular, storage disorders (for example, urinary incontinence) as well as bladder underactivity—are major health-related problems that increase with age. Yet lower urinary tract symptoms remain under-diagnosed and poorly managed, and incontinence has been cited as the major reason for institutionalization in elderly populations and is one of the most common conditions in primary care practice. Although lifestyle and behavior therapy has been used as a useful treatment regimen for urge incontinence, medications (often used as adjunct) can provide additional benefit. This review will include current therapies used for treatment of urinary incontinence.