Pudendal Nerve Stimulation Research Articles

Current role of neuromodulation in bladder pain syndrome/interstitial cystitis.

Neuromodulation is recommended by major international guidelines as a fourth-line treatment in bladder pain syndrome/interstitial cystitis (BPS/IC) patients after failure of behavioural, oral and intravesical pharmacological treatments, including hydrodistension. A non-systematic review of studies identified by electronic search of MEDLINE was performed with no time limitation. A narrative synthesis of the existing evidence regarding the results of sacral, tibial and pudendal nerve stimulation in the management of BPS/IC was developed. Neuromodulation in pelvic chronic pain disorders, including BPS/IC, is a useful tool for refractory patients to conventional treatments. Sacral neuromodulation may be effective in patients with BPS without Hunner's lesions, and the effect seems to be maintained in the mid- and long-term. Posterior tibial nerve stimulation can be offered to patients with BPS/IC in the context of a multidisciplinary approach. When pudendal neuralgia is suspected, selective pudendal nerve stimulation has a high response rate. The aetiology of the pain can influence the outcomes in the mid- and long-term of the different neuromodulation approaches, thus careful diagnosis is recommended.

Transcutaneous pudendal nerve stimulation for refractory urinary incontinence: A viable option?

AbstractAccording to international recommendations pelvic floor exercises represent the first conservative intervention to be offered to patients with non‐neurogenic urinary incontinence. Transcutaneous electrical stimulation of the pudendal nerve using sticking electrodes has not been extensively studied so far and is not mentioned in the European guidelines. Physiology suggests that it might be a viable option to treat incontinence refractory to pelvic floor exercises. To investigate the effects of transcutaneous electrical stimulation of the pudendal nerve in a sample of patients of both genders with urinary incontinence refractory to pelvic muscle exercises. Prospective pilot study on a convenience sample, assessed with 24 h pad‐test. Twenty‐four patients (18 male, six female) were enrolled. Pre‐treatment urinary leakages with sacral root stimulation were Me = 230 g, IQR [90;305], range 50–500. Post‐treatment urinary leakages had a median of 55 g, IQR [10;137], range 0–400 (p < 0.0001). Transcutaneous pudendal nerve stimulation is an effective, non‐invasive treatment that deserves studies on larger samples.

MP08-16 LOW PRESSURE VOIDING INDUCED BY PUDENDAL NERVE STIMULATION AND BLOCK USING LEAD ELECTRODES IN CATS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology (MP08)1 Sep 2021MP08-16 LOW PRESSURE VOIDING INDUCED BY PUDENDAL NERVE STIMULATION AND BLOCK USING LEAD ELECTRODES IN CATS Jialiang Chen, Jianan Jian, Jicheng Wang, Zhijun Shen, Bing Shen, William Wang, Jonathan Beckel, William C de Groat, Christopher Chermansky, and Changfeng Tai Jialiang ChenJialiang Chen More articles by this author , Jianan JianJianan Jian More articles by this author , Jicheng WangJicheng Wang More articles by this author , Zhijun ShenZhijun Shen More articles by this author , Bing ShenBing Shen More articles by this author , William WangWilliam Wang More articles by this author , Jonathan BeckelJonathan Beckel More articles by this author , William C de GroatWilliam C de Groat More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , and Changfeng TaiChangfeng Tai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001981.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We have previously shown that detrusor sphincter dyssynergia (DSD) in spinal cord injured (SCI) cats can be blocked with high frequency, biphasic, bilateral stimulation of the pudendal nerves using cuff electrodes. Also, we showed that combining this block with lower frequency (30 Hz) unilateral pudendal nerve stimulation (PNS) resulted in low-pressure (≤50 cmH2O) voiding in SCI cats. In this experiment, we sought to determine whether wire lead electrodes could be used to block and stimulate the pudendal nerve in spinal intact cats to achieve low-pressure voiding. METHODS: In anesthetized cats, wire lead electrodes were placed on both pudendal nerves. High frequency biphasic stimulation (1 kHz) was applied to block the nerve while 30 Hz stimulus pulses (0.2 ms) applied by a separate lead electrode located proximally on the nerve was used to elicit contractions of the external urethral sphincter (EUS) or induce a reflex bladder contraction. In 4 cats, a catheter was inserted into the distal urethra to perfuse and measure the increase in urethral pressure (IUP) caused by EUS contraction. In another 4 cats, intravesical pressure was measured via a catheter inserted into the bladder dome. RESULTS: The 1 kHz stimulation (30-60 secs, 0.5-5 mA) produced a complete post-stimulation block of PNS evoked IUP for ≥2 mins (see figure 1) and a partial block lasting 6-18 minutes. The block duration lengthened after increasing either the intensity or duration of the kHz stimulation. Without the 1 kHz block, 30 Hz stimulation alone induced high-pressure (90 cmH2O) voiding (see figure 2). When combined with the 1 kHz block, the 30 Hz stimulation induced low-pressure (≤50 cmH2O) voiding with a voiding efficiency of 80%. CONCLUSIONS: This study demonstrated that the pudendal nerve can be successfully blocked by a lead electrode. Furthermore, combining 1 kHz PNS, which blocks EUS contractions, and 30 Hz PNS, which stimulates the bladder, results in low-pressure voiding that is highly efficient. Source of Funding: Bridging the Gap Plus (BG+) program of DARPA under contract N66001-20-C-4050 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e156-e157 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jialiang Chen More articles by this author Jianan Jian More articles by this author Jicheng Wang More articles by this author Zhijun Shen More articles by this author Bing Shen More articles by this author William Wang More articles by this author Jonathan Beckel More articles by this author William C de Groat More articles by this author Christopher Chermansky More articles by this author Changfeng Tai More articles by this author Expand All Advertisement Loading ...

PD36-12 STIMWAVE® FOR PUDENDAL NEURALGIA

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (PD36)1 Sep 2021PD36-12 STIMWAVE® FOR PUDENDAL NEURALGIA Ly Hoang Roberts, Annah Vollstedt, Josh Volin, Teresa McCartney, and Kenneth Peters Ly Hoang RobertsLy Hoang Roberts More articles by this author , Annah VollstedtAnnah Vollstedt More articles by this author , Josh VolinJosh Volin More articles by this author , Teresa McCartneyTeresa McCartney More articles by this author , and Kenneth PetersKenneth Peters More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002040.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with pudendal neuralgia refractory to traditional therapies, prior studies have shown efficacy in chronic stimulation with Interstim® (Medtronic, Inc., Minneapolis, MN). This study reports on a wireless system to power an implanted lead at the pudendal nerve, StimWave®, to treat pudendal neuralgia. METHODS: Retrospective chart review identified patients with a lead placed at the pudendal nerve for neuralgia and powered wirelessly. Clinical outcomes were assessed at post-operative visits and phone calls. Administered non-validated follow-up questionnaire evaluated the GRA, percentage of pain improvement, satisfaction with device, and initial and current settings of the device (hours/day of stimulation). RESULTS: Thirteen patients had the StimWave® lead placed at the pudendal nerve, 12 (92%) female and 1 (7.6%) male. Mean age was 50 years (range: 20-58). Failed prior therapies include medical therapy (100%), pelvic floor physical therapy (PFPT) (92%), pudendal nerve blocks (85%), pelvic floor muscle trigger point injections (69%), neuromodulation (30.7%), or surgeries for urogenital pain (23.1%). After the trial period, 10/13 (76.9%) had >50% improvement in pain with 6/13 (46.1%) reporting 100% pain improvement. Nine underwent permanent lead placement. At last post-operative visit (range 6-83 d), 4/9 patients reported >50% pain improvement. Seven patients reached for phone calls (8-734 d) reported symptoms to be "markedly improved" (n=2; 28.6%), "moderately improved" (n =4; 57.1%,), or "slightly improved" (n=1; 14.3%). Over half (5/7) reported complications including lead migration (n=2), broken wire (n=1) or non-functioning antenna (n=2). CONCLUSIONS: Complex patients with refractory pudendal neuralgia may benefit from pudendal nerve stimulation via StimWave. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e600-e600 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ly Hoang Roberts More articles by this author Annah Vollstedt More articles by this author Josh Volin More articles by this author Teresa McCartney More articles by this author Kenneth Peters More articles by this author Expand All Advertisement Loading ...

Mapping afferent and pelvic postganglionic neurons of the urethra from female rats: The L6 DRG is the major primary afferent supplier.

To map sensory and pelvic postganglionic neurons from three different regions of the female rat urethra. The neuronal tracer True Blue (TB) was injected into the pre-pelvic, pelvic, and clitoral regions of the urethra from female Wistar rats. Seven days after TB injection, TB+ cells from the dorsal root ganglia (DRGs) and the major pelvic ganglion (MPG) were examined. The number and morphometry of TB+ cells were determined. TB+ cells were mainly distributed in lumbar 1 (L1), lumbar 2 (L2), lumbar 6 (L6), and sacral 1 (S1) DRGs, and in the MPG. The mean number of sensory neurons was 1200 ± 143. TB injection in pre-pelvic and pelvic urethra labeled neurons in L1, L2, L6, and S1 DRGs. TB injection in clitoral urethra labeled neurons in L6 and S1 DRGs. L6 DRG contained >50% of the total urethral TB+ neurons, and ~80% of the clitoral region. The mean value of the total number of MPG TB+ neurons was 1217 ± 72. DRG and MPG neurons projecting to the urethra presented a somatotopic distribution. The results demonstrated that L6 DRG is the major supplier of afferent innervation to the urethra, and that the distal urethral region is exclusively innervated by lower lumbosacral DRGs. Considering that electrical stimulation of sensory pudendal nerve improves overactive bladder, and that most of the sensory neurons in the distal urethra are from L6 DRG, electrical stimulation of this ganglion may be an innovative and effective neuromodulation therapy for neurogenic urinary dysfunctions.

Short-term Efficacy and Mechanism of Electrical Pudendal Nerve Stimulation Versus Pelvic Floor Muscle Training Plus Transanal Electrical Stimulation in Treating Post-radical Prostatectomy Urinary Incontinence

To assess the short-term efficacy of electrical pudendal nerve stimulation (EPNS) versus pelvic floor muscle training (PFMT) plus transanal electrical stimulation (TES) for the early treatment of post-radical prostatectomy urinary incontinence (PRPUI) and explore its mechanism of action. A parallel designed randomized controlled trial was conducted at a research institute and a university hospital. Ninety-six PRPUI patients were allocated to EPNS group (64 cases) and PFMT+TES group (32 cases) and treated by EPNS and biofeedback-assisted PFMT plus TES, 3 times a week for 8 weeks, respectively. Outcome measurements were improvement rate, scores of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the number of used diapers. After 24 treatments, the efficacy rate of 68.7% in EPNS group was significantly higher than that of 34.4% in PFMT+TES group (P=0.005). The ICIQ-UI SF score, and urine leakage amount score, diaper score, symptom and quality of life improved significantly in both groups and showed Therapy x Treatment interaction, and the above scores in EPNS group were significantly lower than these in PFMT+TES group. Perineal ultrasonographic recordings showed that PFM movement amplitude during EPNS (≥1- <3 mm) was similar to that during PFMT, however, PFM movement EMG amplitude was significantly higher during EPNS than during PFMT (P <0.001). EPNS is more effective than PFMT+TES in short-term (8 weeks) treatments of early urinary incontinence after radical prostatectomy. Its mechanism of action is that EPNS can excite the pudendal nerve and simulate PFMT.

Initial experience using a novel nerve stimulator for the management of pudendal neuralgia.

In patients with pudendal neuralgia, prior studies have shown efficacy in chronic stimulation with Interstim® (Medtronic, Inc.). This feasibility study reports on the initial experience of using a wireless system to power an implanted lead at the pudendal nerve, StimWave®, to treat pudendal neuralgia. Retrospective chart review identified patients with a lead placed at the pudendal nerve for neuralgia and powered wirelessly. Clinical outcomes were assessed at Postoperative visits and phone calls. Administered non-validated follow-up questionnaire evaluated the Global Response Assessment, percentage of pain improvement, satisfaction with device, and initial and current settings of the device (h/day of stimulation). Thirteen patients had the StimWave® lead placed at the pudendal nerve, 12 (92%) female and 1 (7.6%) male. Mean age was 50 years (range: 20-58). Failed prior therapies include medical therapy (100%), pelvic floor physical therapy (92%), pudendal nerve blocks (85%), pelvic floor muscle trigger point injections (69%), neuromodulation (30.7%), or surgeries for urogenital pain (23.1%). After the trial period, 10/13 (76.9%) had >50% improvement in pain with 6/13 (46.1%) reporting 100% pain improvement. Nine underwent permanent lead placement. At last postoperative visit (range, 6-83 days), 5/9 patients reported >50% pain improvement. Seven patients reached for phone calls (22-759 days) reported symptoms to be "markedly improved" (n = 2), "moderately improved" (n = 4), or "slightly improved" (n = 1). At follow up, complications included lead migration (n = 2), broken wire (n = 1), or nonfunctioning antenna (n = 2). Complex patients with pudendal neuralgia may benefit from pudendal nerve stimulation via StimWave®.

Tetanic stimulation of the pudendal nerve prior to transcranial electrical stimulation augments the amplitude of motor evoked potentials during pediatric neurosurgery.

Reportedly, tetanic stimulation prior to transcranial electrical stimulation (TES) facilitates elicitation of motor evoked potentials (MEPs) by a mechanism involving increased corticomotoneuronal excitability in response to somatosensory input. However, the posttetanic MEP following stimulation of a pure sensory nerve has never been reported. Furthermore, no previous reports have described posttetanic MEPs in pediatric patients. The aim of this study was to investigate the efficacy of posttetanic MEPs in pediatric neurosurgery patients and to compare the effects on posttetanic MEP after tetanic stimulation of the sensory branch of the pudendal nerve versus the standard median and tibial nerves, which contain a mixture of sensory and motor fibers. In 31 consecutive pediatric patients with a mean age of 6.0 ± 5.1 years who underwent lumbosacral surgery, MEPs were elicited by TES without tetanic stimulation (conventional MEPs [c-MEPs]) and following tetanic stimulation of the unilateral median and tibial nerves (mt-MEPs) and the sensory branch of the pudendal nerve (p-MEP). Compound muscle action potentials were elicited from abductor pollicis brevis (APB), gastrocnemius (Gc), tibialis anterior (TA), and adductor hallucis (AH) muscles. The success rate of monitoring each MEP and the increases in the ratios of mt-MEP and p-MEP to c-MEP were investigated. The success rate of monitoring p-MEPs was higher than those of mt-MEPs and c-MEPs (87.5%, 72.6%, and 63.3%, respectively; p < 0.01, adjusted by Bonferroni correction). The mean increase in the ratio of p-MEP to c-MEP for all muscles was significantly higher than that of mt-MEP to c-MEP (3.64 ± 4.03 vs 1.98 ± 2.23, p < 0.01). Subanalysis of individual muscles demonstrated significant differences in the increases in the ratios between p-MEP and mt-MEP in the APB bilaterally, as well as ipsilateral Gc, contralateral TA, and bilateral AH muscles. Tetanic stimulation prior to TES can augment the amplitude of MEPs during pediatric neurosurgery, the effect being larger with pudendal nerve stimulation than tetanic stimulation of the unilateral median and tibial nerves. TES elicitation of p-MEPs might be useful in pediatric patients in whom it is difficult to elicit c-MEPs.

The short-term efficacy of electrical pudendal nerve stimulation versus intravesical instillation for the urethral pain syndrome: a randomized clinical trial.

Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS). Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score. The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant. Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention. ClinicalTrials.gov (NCT03671993).

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether 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 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether 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, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive 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.

Bilateral electrical pudendal nerve stimulation as additional therapy for lower urinary tract dysfunction when stage II sacral neuromodulator fails: a case report

BackgroundSacral neuromodulation (SNM) has become an effective therapy for patients with lower urinary tract dysfunction (LUTD) who do not respond to conservative treatment. However, an effective treatment strategy for patients who fail SNM has not yet been identified. An option for LUTD is needed when the clinical response to the SNM diminishes.Case presentationA 51-year-old Chinese man presented to an outpatient clinic complaining of difficulty in urination for > 3 years. The patient also complained of urinary frequency and urgency, accompanied by perineal discomfort. He was diagnosed with LUTD based on his symptoms and previous examinations. The patient underwent sacral neuromodulation with a permanent implantable pulse generator (IPG) (provided free of charge by Chengnuo Medical Technology Co., Ltd.; General Stim, Hangzhou, China) in the left buttock, as he participated in the company’s clinical trial to test the long-term effects of IPG. He reported loss of efficacy of the device 3 months after the implantation. We performed bilateral electrical pudendal nerve stimulation (EPNS) therapy for him. After 2 weeks of treatment, he began to report smooth voiding within 2 h after EPNS, and a moderate improvement in urinary frequency, urgency, and perineal discomfort. After 4 weeks of EPNS, the patient reported > 50% improvement in his urination, evaluated with the short form of the International Consultation on Incontinence Questionnaire for Male Lower Urinary Tract Symptoms. He reported smooth voiding, moderate improvements in urinary frequency and urgency, and the disappearance of the perineal discomfort. He also reported improved sleep and erections. The patient was discharged after 8 weeks of EPNS treatment.ConclusionEPNS could be an option as an additional therapy for patients with LUTD who have failed SNM.

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation

Neurogenic bladder management after spinal cord injury (SCI) is very challenging. Daily urethral catheterization is most commonly used to empty the bladder, which causes frequent infections of the lower urinary tract. This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13–14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40–50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20–30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal nerves bilaterally with 10 kHz stimulation to relax the external urethral sphincter and reduce the urethral outlet resistance successfully induced highly efficient (average 80–100%), low pressure (<50 cmH2O) voiding. The PNS at 5 Hz also promoted urine storage by inhibiting reflex bladder activity and increasing bladder capacity. At the end of 14-week chronic testing, low pressure efficient voiding induced by PNS was further confirmed under anesthesia by directly measuring voiding pressure using a bladder catheter inserted through the bladder dome. This study demonstrated the efficacy and safety of the PNS in awake chronic SCI cats, suggesting that a novel neuroprosthesis can be developed for humans to restore bladder function after SCI by stimulating and/or blocking the pudendal nerves.

State-dependent bioelectronic interface to control bladder function

Electrical stimulation therapies to promote bladder filling and prevent incontinence deliver continuous inhibitory stimulation, even during bladder emptying. However, continuous inhibitory stimulation that increases bladder capacity (BC) can reduce the efficiency of subsequent voiding (VE). Here we demonstrate that state-dependent stimulation, with different electrical stimulation parameters delivered during filling and emptying can increase both BC and VE relative to continuous stimulation in rats and cats of both sexes. We show that continuous 10 Hz pudendal nerve stimulation increased BC (120–180% of control) but decreased VE (12–71%, relative to control). In addition to increasing BC, state-dependent stimulation in both rats and cats increased VE (280–759% relative to continuous stimulation); motor bursting in cats increased VE beyond the control (no stimulation) condition (males: 323%; females: 161%). These results suggest that a bioelectronic bladder pacemaker can treat complex voiding disorders, including both incontinence and retention, which paradoxically are often present in the same individual.

Conundrum of chronic pelvic pain and a pelvic journey of unparalleled grit: The good, the bad, and the ugly

Conundrum of chronic pelvic pain and a pelvic journey of unparalleled grit: The good, the bad, and the ugly

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.

Pudendal neuromodulation for pelvic pain

Current literature regarding the role of neuromodulation for the treatment of pelvic pain will be addressed with a focus on pudendal neuromodulation. The mechanism of action for pudendal nerve stimulation and technique for pudendal neuromodulation will be reviewed. Literature regarding the efficacy of neuromodulation for the treatment of pelvic pain will be summarized. Multiple studies have demonstrated efficacy of various modalities of neuromodulation in the treatment of chronic pelvic pain. Neuromodulation may be an effective treatment option for the treatment of chronic pelvic pain, with studies showing a reduction of pain and an improvement in quality of life with various neuromodulation modalities. However, the quality of these studies is generally poor and further large-scale, randomized controlled trials are required.

Medications used to treat bladder disorders may alter effects of neuromodulation.

Neuromodulation (nerve stimulation) can produce analgesia. One form, bilateral pudendal nerve stimulation (bPNS), suppresses responses to urinary bladder distension (UBD) in hypersensitive rats. Drugs can modify this effect (eg, benzodiazepines, but not opioids, suppress bPNS effects). Prior to a clinical trial of bPNS effects on bladder pain, we felt it was prudent to survey the effects of medications commonly used in patients with bladder disorders. Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Antimuscarinic (oxybutynin), β3 -adrenoceptor agonist (mirabegron, CL316243), α1 -adrenoceptor antagonist (tamsulosin), antidepressant (amitriptyline), muscle relaxing (baclofen), and sedative (propofol) agents were administered and effects of bPNS on responses to UBD assessed. bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses) were used as nociceptive endpoints. Many of these drugs directly inhibited the VMRs to UBD, but only mirabegron, at the doses employed, significantly reduced inhibitory effects of bPNS. In the presence of the other drugs, bPNS continued to produce statistically significant inhibition of VMRs to UBD. This study suggests that concurrent therapy with drugs used to treat bladder disorders could affect assessment of the effects of bPNS on bladder hypersensitivity. This study gives guidance to clinical trials using bPNS for the treatment of painful bladder syndromes and suggests potential clinical use of some of these medications in the treatment of these same disorders.

Benzodiazepines Suppress Neuromodulatory Effects of Pudendal Nerve Stimulation on Rat Bladder Nociception.

Neuromodulation, as a therapeutic modality for pain treatment, is an alternative to opioid therapies and therefore receiving increased interest and use. Neuromodulation at a peripheral nerve target, in the form of bilateral electrical pudendal nerve stimulation (bPNS), has been shown to reduce bladder hypersensitivity in rats and anecdotally reduces pain in humans with pelvic pain of urological origin. Recent studies have identified a role for spinal γ-aminobutyric acid (GABA) receptors in this effect. Concomitant medication use, such as benzodiazepines, could alter responses to neuromodulation, and so before the development of a clinical trial to confirm translation of this potential therapy, the potential interactions between acute and chronic use of benzodiazepines and bPNS were examined in a preclinical model. Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Diazepam (1-5 mg/kg intraperitoneal [i.p.]) or vehicle was administered acutely (with or without bPNS) and chronically (5 mg/kg subcutaneous [s.c.] daily for 2 weeks before the final experiment). bPNS was delivered as bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses to urinary bladder distension [UBD]) were used as nociceptive end points. Due to the profound effects of diazepam, the effect of midazolam (0.5-1.0 mg/kg i.p.) on VMRs and bPNS effects was also studied. Diazepam and midazolam both produced a dose-dependent, flumazenil-reversible inhibition of VMRs to UBD. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that had received vehicle injections. Select doses of diazepam and midazolam suppressed the inhibitory effect of bPNS on VMRs. This study suggests that inhibitory effects of bPNS on bladder pain could be suppressed in subjects receiving benzodiazepine therapy, suggesting that potential clinical testing of pudendal nerve stimulation for the treatment of painful bladder syndromes may be confounded by the use of benzodiazepines. Clinical assessment of other forms of neuromodulation should also be screened for impacts of benzodiazepines.

Additive Inhibition of Reflex Bladder Activity Induced by Bilateral Pudendal Neuromodulation in Cats.

ObjectiveTo determine the inhibitory effect on bladder activity induced by bilateral pudendal neuromodulation.MethodsIn 10 cats under anesthesia, two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves for stimulation. A double lumen catheter was inserted into the bladder through the urethra to infuse saline and measure bladder pressure. During repeated cystometrograms (CMGs) pudendal nerve stimulation (PNS: 5 Hz, 0.2 ms, 5–15 min) was applied unilaterally or bilaterally at 1- or 2-times intensity threshold (T) for inducing anal sphincter twitching. PNS inhibition was indicated by the increase in bladder capacity measured by CMGs.ResultsUnilateral PNS at 1T did not significantly increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 30%. Bilateral PNS at 1T also failed to increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 60%, indicating an additive effect induced by the bilateral 2T PNS. Unilateral 1T PNS did not enhance the inhibitory effect induced by contra-lateral 2T PNS.ConclusionThis study in anesthetized cats reveals that an additive inhibition of reflex bladder activity can be induced by bilateral pudendal neuromodulation, indicating that bilateral PNS might achieve better therapeutic efficacy in treating overactive bladder (OAB) than unilateral PNS.

Neuromodulatory effects of pudendal nerve stimulation on bladder hypersensitivity are present in opioid-pretreated rats

Background and objectivesBilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models and anecdotally reduces pain in humans with pelvic pain of urologic origin. Concomitant opioids are known...