Mapping a Danger Zone of the Dorsal Nerve of the Clitoris: Implications in Female Cosmetic Genital Surgery.

BACKGROUND: The literature regarding the route of the dorsal nerve of the clitoris is sparse and lacks surgical focus. With an increasing number of procedures being performed on the labia, it is important to elucidate the route and note any variation from normal of the nerve. METHODS: Fifty-one cadavers were dissected to yield 97 dorsal nerve of the clitoris samples. Measurements were taken from (1) the dorsal nerve of the clitoris penetration point of the perineal membrane to the urethra, (2) the nerve's penetration point of the perineal membrane to the pubic bone, (3) the angle of the clitoris to the branch point of the dorsal nerve of the clitoris, and (4) the branch point of the nerve to the distalmost point of the glans clitoris. Any anomalous branching patterns of the dorsal nerve of the clitoris were recorded and classified. RESULTS: The means and standard deviations of each measurement were used to create a surgical danger zone. The mean of each measurement was (1) 34.63 mm, (2) 5.74 mm, (3) -3.07 mm, and (4) 30.40 mm, respectively. In addition, six distinct branching patterns were observed, organized, and classified based on the location and number of branches observed. CONCLUSIONS: The dorsal nerve of the clitoris has multiple branching patterns and typically travels along the same course in most women. Further investigation of the course and three-dimensional position of the dorsal nerve of the clitoris is warranted to preserve sexual sensation as the frequency of procedures involving the female pudendum increases.

The pudendal nerve motor branch regenerates via a brain derived neurotrophic factor mediated mechanism.

Peripheral nerve injuries can significantly reduce quality of life. While some recover, most do not recover fully, resulting in neuropathic pain and loss of sensation and motor function. Research on the mechanisms of peripheral nerve regeneration could elucidate poor patient outcomes and potential treatments. This study was designed to determine if brain derived neurotrophic factor (BDNF) is necessary for pudendal nerve regeneration and functional recovery. Peripheral administration of tyrosine kinase B functional chimera (TrkB) was used to inhibit the BDNF regenerative pathway. Female Sprague-Dawley rats received tyrosine kinase B functional chimera (TrkB) or saline after a pudendal nerve crush (PNC) or Sham PNC and were divided into three groups: Sham PNC, PNC + Saline, and PNC + TrkB. Seven days after injury, relative ßII tubulin expression (1.0 ± 0.2) was significantly decreased after PNC + TrkB compared to PNC + saline (2.9 ± 1.0). Three weeks after injury, BDNF plasma concentration (1320.8 ± 278.1 pg/ml) was significantly reduced in PNC + TrkB compared to PNC + saline rats (2053.4 ± 211.0 pg/ml). Pudendal nerve motor branch firing rate (54.0 ± 9.5 Hz) was significantly decreased in the PNC + TrkB group compared to the PNC + saline group (120.4 ± 17.1 Hz); while nerve firing rate of the PNC + saline group was not significantly different from sham PNC rats (121.8 ± 26.6 Hz). This study demonstrated that peripheral administration of TrkB bound free BDNF and inhibited the regenerative response after PNC. BDNF is necessary for normal PN motor branch recovery after PNC.

Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction.

BACKGROUND: Although pelvic floor dysfunction (PFD) has a multifactorial etiology, pregnancy and childbirth are considered crucial events predisposing to urinary incontinence as well as pelvic organ prolapse, which are highly prevalent. Rats are the most frequently used animal model and pudendal nerve crush (PNC) and vaginal distension (VD) are often used to mimic vaginal delivery. OBJECTIVE: To document the time course of events after simulated vaginal delivery (SVD) on the urethral sphincter and the vaginal smooth muscle layer. MATERIALS AND METHODS: Virgin female Sprague-Dawley rats were subjected to SVD (PNC + VD) or sham surgery and evaluated at 7, 14, 21, and 42 days after the injury. Urethral function was determined in vivo by microultrasound during cystometry and vaginal smooth muscle layer was harvested for in vitro pharmacologic investigation by isometric tension recording. Furthermore, vaginal and urethral samples were investigated by immunohistochemistry and real-time quantitative polymerase chain reaction. RESULTS: Microultrasound showed no bursting of the urethral sphincter in the SVD group at 7 days with a functional recovery starting at 14 days, and normal bursting at 21 and 42 days. Vaginal smooth muscle showed higher sensitivity to carbachol at 14 and 21 days after injury; however, at 42 days, its sensitivity decreased when compared with sham. CONCLUSION: SVD induces urethral dysfunction and a shift in vaginal smooth muscle contractile responses to carbachol.

Low-intensity pulsed ultrasound for regenerating peripheral nerves: potential for penile nerve.

Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.

Vacuum therapy prevents corporeal veno-occlusive dysfunction and penile shrinkage in a cavernosal nerve injured rat model.

Erectile dysfunction and penile shrinkage are the common complications after radical prostatectomy. Penile rehabilitation is widely applied after the surgery. Vacuum therapy is one of the three penile rehabilitation methods used in the clinical setting, but its mechanism is not well known. This study was designed to investigate whether vacuum erectile device (VED) can prevent corporeal veno-occlusive dysfunction and penile shrinkage in the bilateral cavernous nerve crush (BCNC) rat model. Adult male Sprague-Dawley rats were randomly assigned into three groups: sham group, BCNC group, and BCNC + VED group. After 4 weeks, penile length and intracavernosal pressure (ICP) were measured, and then the middle part of the penis was harvested after dynamic infusion cavernosometry to complete the following items: smooth muscle/collagen ratios and collagen I/III ratios; ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell; and the expression of calponin-1 and osteopontin. The penile shortening, peak ICP and ICP drop rate after alprostadil injection were significantly improved with vacuum therapy after 4-week treatment. Compared with BCNC group, VED significantly increased smooth muscle/collagen ratios, decreased collagen I/III ratios, and preserved the ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell. The data also showed that animals exposed to VED could partially reverse the expression of calponin-1 and osteopontin induced by BCNC. In conclusion, vacuum therapy is effective to prevent penile shrinkage and veno-occlusive dysfunction in penile rehabilitation, which may be associated with well-preserved structure and function of the tunica albuginea, endothelial cell, and smooth muscle cell.

Neuropathic painful complications due to endopelvic nerve lesions after robot-assisted laparoscopic prostatectomy: Three case reports.

RATIONALE: Robot-assisted laparoscopic prostatectomy (RALP) is the most frequent strategy used for the surgical remedy of patients with localized prostate cancer. Although there is awareness about potential patient positioning nerve injuries, iatrogenic nerve lesions are less described in the literature. Here, we report 3 cases of patients who presented with neuropathic painful complications due to RALP-associated nerve lesions. PATIENT CONCERNS: A 62-year-old patient (case 1), a 72-year-old male (case 2), and a 57-year-old patient (case 3) presented at the clinic with symptoms of neuropathic pain after RALP surgery. DIAGNOSIS: Patients were diagnosed with a potential injury of different branches of the pudendal nerve (cases 1 and 2), and left obturator nerve (case 3). INTERVENTIONS: Patients underwent multimodal pharmacologic treatment through pregabalin, weak opioids, strong opioid, paracetamol, and adjuvants. In cases 2 and 3, a multidisciplinary approach was needed. As the patients responded to conservative treatment, invasive approaches were not necessary. OUTCOMES: After treatment, the patients of case 1 showed pain relief after 4 days, paresthesia resolved in 15 days, whereas the anal crushing sensation lasted for approximately 1 month. In case 2, after 4 weeks of treatment, the patient experienced a considerable decrement in pain intensity with complete response after 4 months. In case 3, pain relief was achieved after 2 days, motor symptoms recovery after 2 weeks, and neuropathic features resolved completely after 5 weeks although the obturator sign resolved within 2 months. LESSONS: The RALP-associated neurologic injuries may occur even when performed by highly experienced surgeons. A better understanding of the potential iatrogenic nerve lesions can surely allow an improvement in the surgical technique. A multidisciplinary approach and early multimodal pain strategy are mandatory for managing these complications.

Perineal Pressure During Hip Arthroscopy Is Reduced by Use of Trendelenburg: A Prospective Study With Randomized Order of Positioning.

BACKGROUND: The use of traction during hip arthroscopy is commonly used to provide safe joint access and to improve visualization. However, traction during hip arthroscopy has been associated with complications ranging from transient neuropraxias to devastating soft-tissue necrosis. Trendelenburg positioning may be helpful, but the degree to which this is true is not well understood. QUESTIONS/PURPOSES: To determine whether there would be a reduction in perineal pressure at 5°, 10°, and 15° of Trendelenburg compared with baseline (0° of Trendelenburg) while in the modified supine position during hip arthroscopy. METHODS: A consecutive cohort of 50 patients treated with hip arthroscopy by a single, high-volume orthopaedic surgeon was analyzed. There were 30 females and 20 males in this study, with a mean age of 36 ± 16 years (range, 14 to 66 years); mean BMI was 26 kg/m. In the operating room, patients were placed in the modified supine position on a traction extension table with a well-padded perineal post. A standard blood pressure cuff was secured to the post to measure pressure exerted on the perineum as traction was applied to distract the hip. For each patient, pressure against the perineum was measured at four different positions using a digital level: 0°, 5°, 10°, and 15° of Trendelenburg. These positions were tested in a random order for each patient. Mean pressure was compared within patients under the four-period crossover design using a repeated-measure (mixed) ANOVA model. Examination of the residual error quantile plot showed that the pressure data followed a normal distribution, making the use of a parametric model appropriate. Tests were made for period and order effects. RESULTS: Compared with baseline (0° or no Trendelenburg) there was a reduction in pressure of 4.4 (15.5%) at 5° of Trendelenburg (p = 0.203), 8 (28%) at 10° of Trendelenburg (p = 0.022) and 13.1 (46%) at 15° (p = 0.006). These results were maintained regardless of the sequence of positions used in each patient (0°, 5°, 10°, 15°). CONCLUSIONS: Trendelenburg positioning of 10° and 15° during hip arthroscopy resulted in decreased perineal pressure compared with the neutral (0°) position. This technique is intended to harness gravity to exert the majority of countertraction while retaining the perineal post as a backup patient stabilizer. Routine introduction of Trendelenburg during hip arthroscopy reduces perineal pressure against the post, which may decrease complications related to traction and perineal pressure. Future studies should assess whether the observed differences in perineal pressure will reduce the frequency of post-related complications after hip arthroscopy. LEVEL OF EVIDENCE: Level II, therapeutic study.

Proctalgia y atrapamiento del nervio pudendo: una asociación por descubrir / Proctalgia and pudendal nerve entrapment: an association to know

Introducción: El síndrome de atrapamiento del nervio pudendo (SANP) es una entidad clínica, poco conocida en el ámbito de la Cirugía General, que comprende un amplio abanico de síntomas urinarios, sexuales y proctológicos. El interés para el cirujano general radica en toda la clínica que pueden presentar estos pacientes en la esfera proctológica. De diagnóstico complejo, exige un tratamiento secuencial que incluye distintas herramientas. El objetivo del presente estudio es exponer el SANP desde el punto de vista de la cirugía general, exponiendo un estudio realizado en pacientes afectos de proctalgia para valorar los resultados en el seguimiento a partir de los seis meses. Métodos: Presentamos un estudio observacional que evalúa 53 pacientes afectos de proctalgia en el contexto de un SANP que han sido sometidos a tratamiento con punción-hidrodistensión corticoideo-anestésica del nervio pudendo y sus ramas terminales, observando su respuesta inmediata en términos clínicos de dolor y en seguimiento a partir de los seis meses. Resultados: De los datos obtenidos de nuestra muestra, se observa que el tratamiento con dichas punciones mejora al 79,25 % de los pacientes en el periodo inmediato tras la punción, y el 39,62 % de los pacientes mantienen dicha mejoría a partir de los seis meses. Conclusiones: Concluimos que ante la presencia de proctalgia, el cirujano debe descartar la existencia de un SANP y que, según nuestro estudio, el tratamiento con punción corticoideoanestésica es una opción eficaz de tratamiento que logra mejorar a un importante porcentaje de pacientes

Introduction: Pudendal nerve entrapment (PNE) is a clinical syndrome, little known in the field of General Surgery, which includes a wide range of urinary, sexual and proctological symptoms. The interest for general surgeons lies in the whole clinical study that these patients may present as regards proctology. Complex diagnosis requires a sequential treatment that includes different tools. The aim of this study is to present PNE from the point of view of general surgery by showing a study carried out in patients with proctalgia to assess the results at follow-up after 6 months. Methods: We present an observational study evaluating 53 proctalgia patients in a PNE context who have undergone hydrocortisone puncture of the pudendal nerve, for anesthetic reasons, and its terminal branches, observing its immediate response in clinical terms of pain and in follow-up as from six months. Results: Based on the data obtained from our sample, it may be seen that the treatment with these punctures improves 79.25% of patients in the period immediately after puncture and 39.62% of patients maintain this improvement after the six months. Conclusions: We conclude that in the presence of proctalgia, surgeons should ignore the presence of PNE and that, according to our study, corticosteroid puncture treatment for anesthesia is an effective treatment option that provides relief to a significant percentage of patients

Incidence of Nerve Injury After Hip Arthroscopy.

INTRODUCTION: Hip arthroscopy is a commonly performed procedure that carries a notable risk of nerve injury secondary to port placement and the use of axial traction. Sensory neurapraxia of the pudendal nerve and the lateral femoral cutaneous nerve is most common; however, sexual dysfunction and sciatic nerve injury has also been reported. Reported incidence of nerve injury ranges between 1.4% and 5% in the literature, but much of these data are based on unsolicited patient concerns. This study aimed to determine the true rate of nerve injury among this patient population through administration of a validated survey at multiple time points. METHODS: A prospective study of all patients undergoing hip arthroscopy requiring traction by a single surgeon at our institution was performed. These cases were the first 100 hip arthroscopies performed in practice by the surgeon. Before surgery, all patients were asked about the presence of neuropathic symptoms including sexual dysfunction through administration of a validated questionnaire. The same questionnaire was then administered at several time points postoperatively: on the day of surgery, on postoperative day 2, at the first follow-up visit, and if symptoms persisted, then at each follow-up appointment until resolution of the symptoms. Overall incidence of nerve injury was then calculated. Subgroup analyses were performed to investigate whether traction time, sex, body mass index (BMI), or technically demanding surgical skills affected the incidence. RESULTS: This study included a total of 100 patients with an average age of 29 (13 to 62) years and an average BMI of 25. Nerve injury was seen in 13 patients with an incidence of 13%. Specific nerves injured included the pudendal (9), lateral femoral cutaneous (2), sciatic (1), and superficial peroneal nerves (1). Subgroup analysis did not demonstrate a notable association between the risk of nerve injury and increased traction time, sex, or increased BMI. The technically demanding surgical skills was associated with a notable decrease in the traction time, but no notable difference in the risk of nerve injury was observed. Most nerve injuries resolved within 2 weeks (8 of 13), and all cases of nerve injury resolved within 9 months. DISCUSSION AND CONCLUSIONS: The incidence of nerve injury after hip arthroscopy may be markedly higher than previously reported; however, resolution seems to occur as previously found in the literature. Patients should be educated regarding the risk of nerve injury during this procedure. LEVEL OF EVIDENCE: Level IV.

Electrical stimulation of the pudendal nerve promotes neuroregeneration and functional recovery from stress urinary incontinence in a rat model.

The pudendal nerve can be injured during vaginal delivery of children, and slowed pudendal nerve regeneration has been correlated with development of stress urinary incontinence (SUI). Simultaneous injury to the pudendal nerve and its target muscle, the external urethral sphincter (EUS), during delivery likely leads to slowed neuroregeneration. The goal of this study was to determine if repeat electrical stimulation of the pudendal nerve improves SUI recovery and promotes neuroregeneration in a dual muscle and nerve injury rat model of SUI. Rats received electrical stimulation or sham stimulation of the pudendal nerve twice weekly for up to 2 wk after injury. A separate cohort of rats received sham injury and sham stimulation. Expression of brain-derived neurotrophic factor (BDNF) and ßII-tubulin expression in Onuf's nucleus were measured 2, 7, and 14 days after injury. Urodynamics, leak point pressure (LPP), and EUS electromyography (EMG) were recorded 14 days after injury. Electrical stimulation significantly increased expression of BDNF at all time points and ßII-tubulin 1 and 2 wk after injury. Two weeks after injury, LPP and EUS EMG during voiding and LPP testing were significantly decreased compared with sham-injured animals. Electrical stimulation significantly increased EUS activity during voiding, although LPP did not fully recover. Repeat pudendal nerve stimulation promotes neuromuscular continence mechanism recovery possibly via a neuroregenerative response through BDNF upregulation in the pudendal motoneurons in this model of SUI. Electrical stimulation of the pudendal nerve may therefore improve recovery after childbirth and ameliorate symptoms of SUI by promoting neuroregeneration after injury.

Injury to the perineal branch of the pudendal nerve in men: Outcomes from surgical resection of the perineal branches.

OBJECTIVE: The objective is to report the outcome of an anterior surgical approach to treat neuroma of the perineal branch of the pudendal nerve (PBPN). PATIENTS AND METHODS: An IRB-approved prospective study enrolled 14 consecutive male patients from 2011 through 2015 who had symptoms of perineal/scrotal pain. Each patient had a successful, diagnostic, pudendal nerve block. The surgical procedure was resection of the PBPN and implantation of the nerve into the obturator internus muscle. Mean age at surgery was 50 ± 15 years. Median duration of pain symptoms was 5.5 years (range 1.2-42.9 years). Mechanisms of injury was exercise (6/14), prostatectomy (4/14), and falls (4/14). Outcomes were the Male Pudendal Pain Functional Questionnaire (MQ), and the Numeric Pain Rating Scale (NPRS). RESULTS: The mean postoperative follow-up was 26 ± 14 months. The MQ demonstrated that after surgery, patients overall had significantly less disability due to pudendal pain (P < .03). The NPRS revealed that pain significantly improved (P < .004). CONCLUSIONS: Resection of the PBPN and implantation of this nerve into the obturator internus muscle significantly relieved men's pelvic pain disability.

Pudendal nerve injury is a relatively common but transient complication of hip arthroscopy.

PURPOSE: Hip arthroscopy is emerging as the standard of care for conditions involving the hip, and has a unique set of complications. The purpose of this review was to identify (1) the crude rate of pudendal nerve injury following hip arthroscopy and (2) the specific factors leading to pudendal nerve injury. METHODS: MEDLINE, EMBASE, and PubMed were searched from database inception to October 2016. Patient demographics, indications, surgical technique, complication rates, treatment approaches, and rehabilitation strategies were extracted. RESULTS: Twenty-four studies (n = 3405) were included, with the majority (66%) of studies being level IV evidence. The mean age was 33.9 ± 9.7 years (range 12-78) and 48.2% were males. Average follow-up was 30.2 ± 19.1 months. 62 patients were reported to have sustained pudendal nerve injury (1.8%) post-operatively, and all resolved within 6 weeks to 3 months. Of the seven studies that reported using a perineal post, 20 patients were diagnosed with pudendal nerve injury (4.3%), in contrast to two studies (189 patients) reporting only 0.5% pudendal nerve injury without the use of perineal post. Two studies commented on time of traction during surgical intervention with mean times of 98 and 68 min with complication rates of 10% and 6.6%, respectively. CONCLUSIONS: Pudendal nerve injury is not uncommon following hip arthroscopy, with a reported rate found in this review of 1.8%. Potential risk factors may include the use of a perineal post and long traction times. All reported cases resolved within 3 months. Patients should be informed of complications related to pudendal nerve injury, which include sexual and urinary dysfunction. LEVEL OF EVIDENCE: Level IV, systematic review of level I-IV studies.

Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence.

BACKGROUND: Fecal incontinence is a common disorder, but its pathophysiology is not completely understood. OBJECTIVE: The aim of this review is to present animal models that have a place in the study of fecal incontinence. DATA SOURCES: A literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in August 2016 revealed 50 articles of interest. Search terms included fecal/faecal incontinence and animal model or specific species. STUDY SELECTION: Articles not describing an animal model, in vitro studies, veterinary literature, reviews, and non-English articles were excluded. MAIN OUTCOME MEASURES: The articles described models in rats (n = 31), dogs (n = 8), rabbits (n = 7), and pigs (n = 4). RESULTS: Different fecal incontinence etiologies were modeled, including anal sphincter lesions (33 articles) ranging from a single anal sphincter cut to destruction of 50% of the anal sphincter by sharp dissection, electrocautery, or diathermy. Neuropathic fecal incontinence (12 articles) was achieved by complete or incomplete pudendal, pelvic, or inferior rectal nerve damage. Mixed fecal incontinence (5 articles) was modeled either by the inflation of pelvic balloons or an array of several lesions including nervous and muscular damage. Anal fistulas (2 articles), anal sphincter resection (3 articles), and diabetic neuropathy (2 articles) were studied to a lesser extent. LIMITATIONS: Bias may have arisen from the authors' own work on fecal incontinence and the absence of blinding to the origins of articles. CONCLUSIONS: Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.

The Pudendal Nerve and Its Branches in Relation to Richter's Procedure.

OBJECTIVE: Variations in the branching pattern of the pudendal nerve (PN) have been described in the literature. This study investigated these variations in order to comment on a safe area for the placement of a Richter's stitch. METHODS: Richter's procedure was performed on nine unembalmed female cadavers and followed by dissection. PN dissections were done on another 20 embalmed female cadavers. Variations in the branching pattern of the PN were noted and the distance between the Richter's stitch placed and the PN/or the inferior rectal nerve (IRN) measured. RESULTS: The IRN entered the gluteal region as a separate structure in 6/29 cases. The separate IRN was found to pass between 4.1 and 14.45 mm medial to the ischial spine in 18/29 cases. In one case, the Richter's stitch was found to pierce the IRN. The distance between the stitch and the PN and/or the IRN ranged from 0 to 17.8 mm. CONCLUSIONS: To minimize the risk of nerve damage or entrapment, the Richter's stitch should be placed >20 mm from the ischial spine. This recommended area should be revised for different population groups, as variations might exist between groups.

Combination histamine and serotonin treatment after simulated childbirth injury improves stress urinary incontinence.

AIMS: Histamine and serotonin-related pharmaceuticals have the potential to modulate micturition and continence. The aim of this study was to determine if treatment with histamine and/or serotonin improves stress urinary incontinence (SUI) in female rats. METHODS: Twenty-six age-matched female rats underwent pudendal nerve crush and vaginal distension (PNC + VD), to produce SUI. One week after injury, rats were treated subcutaneously with saline, histamine (1.1 µg), serotonin (2µg), or the combination of both twice daily for another week. A sham injured group received sham PNC + VD and were treated with saline (n = 7). Leak point pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography (EMG) was conducted 2 weeks after injury. The urethra was harvested for qualitative and quantitative histology. Data were analyzed with a one-way ANOVA and Student-Newman-Keuls posthoc test with P < 0.05 indicating statistically significant differences between groups. RESULTS: Combination treatment significantly increased LPP after PNC + VD compared to injured sham treatment and treatment with either histamine or serotonin alone. Compared to injured sham treated rats, all three treatments significantly increased EUS EMG amplitude at both baseline and peak pressure and EUS EMG firing rate at peak pressure during LPP testing. There were more consistent urethral striated muscle fibers and thicker smooth and striated muscle with combination and histamine treatment. There was a statistically significant shift to a greater proportion of thicker collagen fibers in the urethra in serotonin and combination treated rats compared with injured sham treated rats. CONCLUSIONS: Combination treatment was the most effective and may provide an effective therapy for SUI. Neurourol. Urodynam. 35:703-710, 2016. © 2015 Wiley Periodicals, Inc.

[EXPERIMENTAL MODELS OF STRESS URINARY INCONTINENCE].

Despite numerous medical and surgical treatment strategies available, the problem of stress urinary incontinence (SUI) in women is still not completely resolved. Continuing research is underway to modify the sling operations and develop new bulk-enhancing agents, including the use of tissue engineering and cell technologies. To evaluate the safety and effectiveness of new methods at the preclinical stage, adequate and reproducible experimental models of SUI in laboratory animals should be used. This article presents analysis of all SUI models described in the scientific literature and the results of an experimental study comparing two primary ways of modeling, based on bilateral pudendal nerve damage in female rats. The experiment results showed that only bilateral electrocoagulation of proximal part of pudendal nerves by the posterior approach ensured a stable and long-term SUI symptoms in animals in the form of leak point pressure reduction in the urodynamic study and increase of the of the urethral lumen according to histomorphometric analysis. The results suggest that an adequate experimental SUI model is urethral rabdomiosphincter denervation by pudendal nerve electrocoagulation by the posterior surgical approach, when the nerve is damaged in the area of its separation from sciatic nerve. In this case stable and reproducible results are obtainable.

Pudendal nerve injury in men with fecal incontinence after radiotherapy for prostate cancer.

BACKGROUND: The precise etiology of fecal incontinence (FI), which occurs frequently following external beam radiotherapy (EBRT) for prostate carcinoma is unknown. It is possibly related to pelvic nerve injury. The aim of this study was to assess the incidence of pudendal nerve dysfunction in men with FI after EBRT for prostate cancer compared to men with FI but no history of EBRT. MATERIAL AND METHODS: Data were evaluated from 74 men with intact anal sphincters on endo-anal ultrasound (17 post-EBRT) who had been investigated for FI at a tertiary center. Wexner incontinence scores, pudendal nerve function, anorectal manometry, and rectal sensitivity were compared between the two patient groups. RESULTS: Post-radiotherapy patients were older (77±6 vs. 62±17 years, p<0.005) and had worse incontinence than those with no history of radiotherapy (Wexner score; 13±3 vs. 8±4; p<0.005). Bilateral pudendal nerve terminal motor latency (PNTML) was abnormal in 87% of radiotherapy versus 22% of non-radiotherapy patients (p<0.001) and the significant difference persisted even after correction for age differences. Anal sphincter pressures and rectal sensitivity for both groups were similar. CONCLUSION: There is a markedly higher incidence of pudendal nerve dysfunction in men with FI after EBRT for prostate cancer compared with men with FI from other etiologies. The increased severity of incontinence in radiotherapy patients is not matched by alterations in either anal sphincter pressures or rectal sensitivity compared to FI in non-ERBT patients.

Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.

Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.

Sacral neuromodulation as a treatment for pudendal neuralgia.

Pudendal neuralgia is a debilitating pain syndrome, and finding long-lasting treatment modalities has been challenging in pain management. The pudendal nerve has sensory and motor functions, and influences autonomic functions. Thus, entrapment or damage of this nerve can have multiple serious implications. The constellation of symptoms which result from injury to this nerve is commonly referred to as pudendal neuralgia. When conservative therapy does not provide adequate pain relief and surgical procedures fail or are not viable options, central and peripheral nerve stimulation can be effective treatment modalities. More recent approaches to treatment include the use of peripheral nerve stimulation through the use of an electrical lead placed next to the pudendal nerve in the ischioanal fossa. Also, epidural stimulation of the conus medullaris and pulsed radiofrequency ablation of the pudendal nerve have been shown to be effective in small patient populations. We present the case of a 36-year-old woman who sustained pudendal nerve injury during a hysterectomy and subsequently developed intractable pelvic pain and pudendal neuralgia. Conservative treatment measures failed, but she obtained excellent results from peripheral nerve stimulator therapy. Permanent implantation consisted of 4 tined Interstim leads, individually placed into the bilateral S3 and S4 foramina. The patient has been followed for approximately 4 years since her procedure, demonstrating increased function as she is able to stand and sit for prolonged periods of time. She has returned to her usual daily activities, including horseback riding. This is the first reported case of transforminal sacral neurostimulation providing excellent relief of pudendal neuralgia related symptoms.