Contribution of pudendal nerve injury to stress urinary incontinence in a male rat model.

Urinary incontinence is a common complication following radical prostatectomy, as the surgery disturbs critical anatomical structures. This study explored how pudendal nerve (PN) injury affects urinary continence in male rats. In an acute study, leak point pressure (LPP) and external urethral sphincter electromyography (EMG) were performed on six male rats with an intact urethra, the urethra exposed (UE), the PN exposed (NE), and after PN transection (PNT). In a chronic study, LPP and EMG were tested in 67 rats 4 days, 3 weeks, or 6 weeks after sham PN injury, PN crush (PNC), or PNT. Urethras were assessed histologically. Acute PNT caused a significant decrease in LPP and EMG amplitude and firing rate compared to other groups. PNC resulted in a significant reduction in LPP and EMG firing rate 4 days, 3 weeks, and 6 weeks later. EMG amplitude was also significantly reduced 4 days and 6 weeks after PNC. Neuromuscular junctions were less organized and less innervated after PNC or PNT at all timepoints compared to sham injured animals. Collagen infiltration was significantly increased after PNC and PNT compared to sham at all timepoints. This rat model could facilitate preclinical testing of neuroregenerative therapies for post-prostatectomy incontinence.

Transvaginal pudendal nerve blocks in patients with pudendal neuralgia: 2-year follow-up results.

PURPOSE: Pudendal neuralgia (PN) is an extremely painful neuropathy of the pudendal nerve resulting in a negative impact on a patient's quality of life. The aim of this study is to evaluate the 2-year outcomes of repetitive doses of the transvaginal pudendal nerve injections (PNI), and to compare the success of the PNI concerning anatomical levels (endopelvic and extrapelvic portion) of the pudendal nerve pathology. METHODS: This retrospective longitudinal cohort study consists of patients with PN diagnosed with the first four essential Nantes criteria. Diagnostic PNI was performed on 67 patients to fulfill the fifth criteria of Nantes. A total of 56 patients who responded to the initial diagnostic PNI underwent therapeutic repeated transvaginal PNIs twice for 3 weeks apart. Mean pain intensity scores were measured using a visual analog scale at the 1st, 3rd, 6th, 12th, and 24th months after the therapeutic blocks were completed. Effectiveness of the PNIs' was defined as ≥ 50% improvement of the initial pain, and relative improvement was defined as 30-50% improvement of the initial pain. Treatment failure was defined as the reduction of the initial pain by less than 30% or the return of the pain to its worst condition. RESULTS: The efficacy of the PNIs significantly declined over time. Pudendal nerve blocks provided a significant decrease in pain scores; however, this decrease lost its strength significantly in the 24th month. The intervention was more effective in entrapments of the pudendal nerve between sacrospinous and sacrotuberous ligaments or below (Level-2) when compared to the injuries in the endopelvic part (Level-1). More than 50% pain reduction continued in five patients with pathology at Level-1 and 24 patients with pathology at Level-2. CONCLUSION: Repeated PNIs could provide a significant decrease in pain scores for both short- and long-term periods. However, the efficacy of the PNIs declined over 2 years. The success of PNIs may be affected by the anatomical level of the nerve injury; therefore, interligamentous pudendal nerve entrapment cases have more benefits than the cases of pudendal nerve entrapment in the endopelvic part. However, it is recommended to perform therapeutic nerve blocks even in patients with suspected endopelvic pudendal nerve pathology before the referral to surgery.

Astragali radix: could it be an adjuvant for oxaliplatin-induced neuropathy?

Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Repeated administrations significantly reduced oxaliplatin-dependent hypersensitivity with 50%HA, the most effective, fully preventing mechanical and thermal hypersensitivity. Ex vivo, 50%HA reduced morphometric and molecular alterations induced by oxaliplatin in peripheral nerve and dorsal-root-ganglia. In the spinal cord and in brain areas, 50%HA significantly decreased activation of microglia and astrocytes. Furthermore, 50%HA prevented the nephro- and hepato-toxicity induced by the anticancer drug. The protective effect of 50%HA did not alter oxaliplatin-induced apoptosis in colon tumors of Pirc rats, an Apc-driven model of colon carcinogenesis. The hydroalcoholic extract (50%HA) of Astragali radix relieves pain and promotes the rescue mechanisms that protect nervous tissue from the damages triggering chronic pain. A safe profile strongly suggests the usefulness of this natural product in oxaliplatin-induced neuropathy.

Anatomical Variants of the Pudendal Nerve Observed during a Transgluteal Surgical Approach in a Population of Patients with Pudendal Neuralgia.

BACKGROUND: Several studies have described the course and anatomical relations of the pudendal nerve. Several surgical nerve decompression techniques have been described, but only the transgluteal approach has been validated by a prospective randomized clinical trial. The purpose of this study was to describe the course of the nerve and its variants in a population of patients with pudendal neuralgia in order to guide the surgeon in the choice of surgical approach for pudendal nerve decompression. OBJECTIVES: In order to support the choice of the transgluteal approach, used in our institution, we studied the exact topography, anatomical relations, and zones of entrapment of the pudendal nerve in a cohort of operated patients. STUDY DESIGN: Observational study. SETTING: University hospital. METHODS: One hundred patients underwent unilateral or bilateral nerve decompression performed by a single operator via a transgluteal approach. All patients satisfied the Nantes criteria for pudendal neuralgia. The operator meticulously recorded zones of entrapment, anatomical variants of the course of the nerve, and the appearance of the nerve in the operative report. RESULTS: One hundred patients and 145 nerves were operated consecutively. Compression of at least one segment of the pudendal nerve (infrapiriform foramen, ischial spine, and Alcock's canal) was observed in 95 patients. The zone of entrapment was situated at the ischial spine between the sacrospinous ligament (or ischial spine) and the sacrotuberous ligament in 74% of patients.Anatomical variants were observed in 13 patients and 15 nerves. Seven patients presented an abnormal transligamentous course of the nerve (sacrotuberous or sacrospinous). A perineal branch of the fourth sacral nerve to the external anal sphincter was identified in 7 patients. In this population of patients with pudendal neuralgia, the pudendal nerve was stenotic in 27% of cases, associated with an extensive venous plexus that could make surgery more difficult in 25% of cases, and the nerve had an inflammatory appearance in 24% of cases. LIMITATIONS: We obviously cannot be sure that the anatomical variants identified in this study can be extrapolated to the general population, as our study population was composed of patients experiencing perineal pain due to pudendal nerve entrapment and their pain could possibly be related to these anatomical variants, especially a transligamentous course of the pudendal nerve. The absence of other prospective randomized clinical trials evaluating other surgical approaches also prevents comparison of these results with those of other surgical approaches. CONCLUSIONS: This is the first study to describe the surgical anatomy of the pudendal nerve in a population of patients with pudendal neuralgia. In more than 70% of cases, pudendal nerve entrapment was situated in the space between the sacrospinous ligament and the sacrotuberous ligament. Anatomical variants of the pudendal nerve were also observed in 13% of patients, sometimes with a transligamentous course of the nerve. In the light of these results, we believe that a transgluteal approach is the most suitable surgical approach for safe pudendal nerve decompression by allowing constant visual control of the nerve.Key words: Surgical, operative technique, pudendal, neuralgia, transgluteal approach.

Pudendal Neuralgia Due to Pudendal Nerve Entrapment: Warning Signs Observed in Two Cases and Review of the Literature.

Pudendal neuralgia is a chronic neuropathic pelvic pain that is often misdiagnosed and inappropriately treated. The Nantes criteria provide a basis for the diagnosis of pudendal neuralgia due to pudendal nerve entrapment. The 5 essential diagnostic criteria are pain situated in the anatomical territory of the pudendal nerve, worsened by sitting, the patient is not woken at night by the pain, and no objective sensory loss is detected on clinical examination. The fifth criterion is a positive pudendal nerve block. We have also clarified a number of complementary diagnostic criteria and several exclusion criteria that make the diagnosis unlikely. When pudendal neuralgia due to pudendal nerve entrapment is diagnosed according to the Nantes criteria, no further investigation is required and medical or surgical treatment can be proposed. Nevertheless, a number of warning signs suggesting other possible causes of pudendal neuralgia must not be overlooked. These warning signs (red flags) are waking up at night, excessively neuropathic nature of the pain (for example, associated with hypoesthesia), specifically pinpointed pain, which can suggest neuroma and pain associated with neurological deficit. In these atypical presentations, the diagnosis of pain due to pudendal nerve entrapment should be reconsidered and a radiological examination should be performed. The 2 cases described in this report (tumor compression of the pudendal nerve) illustrate the need to recognize atypical pudendal neuralgia and clarify the role of pelvic magnetic resonance imaging (MRI), as MRI provides very valuable information for the evaluation of diseases involving the ischiorectal fossa. The presence of red flags must be investigated in all cases of pudendal neuralgia to avoid missing pudendal neuralgia secondary to a mechanism other than nerve entrapment.

Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.

PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.

[Non-infectious cystalgias]. / Cystalgies non infectieuses.

The trophicity of women's urogenital tissues depends on the hormone level and on the quality of the vaginal flora. Stresses of these mucous membranes, seemingly minor, give rise to complaints of a perceived perineal discomfort, which is disproportionate to the causes. Population in Occident has access to the best medical care and hygiene conditions ever. Yet, expenditures on treatment of these minor disorders are unwarranted. Cystalgia leads to a large number of consultations to general practitioner, gynaecologist and urologist. The aging of our societies is another reason. While life expectancy was 51 in 19th century, it is now 83. Women will now live a third of their life after menopause'. Complaints due to these hormonal withdrawal symptoms need to be heard as they are leading to specific psychological behaviours, which are disconcerting for the clinician. Patients will strive by all means to obtain treatments which are often inappropriate and which sometimes entails the risk of evolving to a chronicity of the pains.

Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury.

BACKGROUND: Intracavernous (IC) injection of stem cells has been shown to ameliorate cavernous-nerve (CN) injury-induced erectile dysfunction (ED). However, the mechanisms of action of adipose-derived stem cells (ADSC) remain unclear. OBJECTIVES: To investigate the mechanism of action and fate of IC injected ADSC in a rat model of CN crush injury. DESIGN, SETTING, AND PARTICIPANTS: Sprague-Dawley rats (n=110) were randomly divided into five groups. Thirty-five rats underwent sham surgery and IC injection of ADSC (n=25) or vehicle (n=10). Another 75 rats underwent bilateral CN crush injury and were treated with vehicle or ADSC injected either IC or in the dorsal penile perineural space. At 1, 3, 7 (n=5), and 28 d (n=10) postsurgery, penile tissues and major pelvic ganglia (MPG) were harvested for histology. ADSC were labeled with 5-ethynyl-2-deoxyuridine (EdU) before treatment. Rats in the 28-d groups were examined for erectile function prior to tissue harvest. MEASUREMENTS: IC pressure recording on CN electrostimulation, immunohistochemistry of the penis and the MPG, and number of EdU-positive (EdU+) cells in the injection site and the MPG. RESULTS AND LIMITATIONS: IC, but not perineural, injection of ADSC resulted in significantly improved erectile function. Significantly more EdU+ ADSC appeared in the MPG of animals with CN injury and IC injection of ADSC compared with those injected perineurally and those in the sham group. One day after crush injury, stromal cell-derived factor-1 (SDF-1) was upregulated in the MPG, providing an incentive for ADSC recruitment toward the MPG. Neuroregeneration was observed in the group that underwent IC injection of ADSC, and IC ADSC treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. CONCLUSIONS: CN injury upregulates SDF-1 expression in the MPG and thereby attracts intracavernously injected ADSC. At the MPG, ADSC exert neuroregenerative effects on the cell bodies of injured nerves, resulting in enhanced erectile response.