Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats.

AIMS: To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). METHODS: Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. RESULTS: All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p < .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups. CONCLUSION: The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.

Stimulation of the pelvic nerve increases bladder capacity in the prostaglandin E2 rat model of overactive bladder.

Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E2 (PGE2) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE2 vs. vehicle and PelN stimulation after intravesical PGE2 on cystometric parameters were quantified. Intravesical infusion of PGE2 resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE2 PelN stimulation reversed the PGE2-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.

The effects of neuromodulation in a novel obese-prone rat model of detrusor underactivity.

Obesity is a global epidemic associated with an increased risk for lower urinary tract dysfunction. Inefficient voiding and urinary retention may arise in late-stage obesity when the expulsive force of the detrusor smooth muscle cannot overcome outlet resistance. Detrusor underactivity (DUA) and impaired contractility may contribute to the pathogenesis of nonobstructive urinary retention. We used cystometry and electrical stimulation of peripheral nerves (pudendal and pelvic nerves) to characterize and improve bladder function in urethane-anesthetized obese-prone (OP) and obese-resistant (OR) rats following diet-induced obesity (DIO). OP rats exhibited urinary retention and impaired detrusor contractility following DIO, reflected as increased volume threshold, decreased peak micturition pressure, and decreased voiding efficiency (VE) compared with OR rats. Electrical stimulation of the sensory branch of the pudendal nerve did not increase VE, whereas patterned bursting stimulation of the motor branch of the pudendal nerve increased VE twofold in OP rats. OP rats required increased amplitude of electrical stimulation of the pelvic nerve to elicit bladder contractions, and maximum evoked bladder contraction amplitudes were decreased relative to OR rats. Collectively, these studies characterize a novel animal model of DUA that can be used to determine pathophysiology and suggest that neuromodulation is a potential management option for DUA.

Sympathetic ß-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

This study investigated the role of the hypogastric nerve and ß-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1-3 mg/kg iv) significantly (P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly (P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly (P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a ß-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition.

Continence and micturition: an anatomical basis.

Urinary incontinence remains an important clinical problem worldwide, having a significant socio-economic, psychological, and medical burden. Maintaining urinary continence and coordinating micturition are complex processes relying on interaction between somatic and visceral elements, moderated by learned behavior. Urinary viscera and pelvic floor must interact with higher centers to ensure a functionally competent system. This article aims to describe the relevant anatomy and neuronal pathways involved in the maintenance of urinary continence and micturition. Review of relevant literature focusing on pelvic floor and urinary sphincters anatomy, and neuroanatomy of urinary continence and micturition. Data obtained from both live and cadaveric human studies are included. The stretch during bladder filling is believed to cause release of urothelial chemical mediators, which in turn activates afferent nerves and myofibroblasts in the muscosal and submucosal layers respectively, thereby relaying sensation of bladder fullness. The internal urethral sphincter is continuous with detrusor muscle, but its arrangement is variable. The external urethral sphincter blends with fibers of levator ani muscle. Executive decisions about micturition in humans rely on a complex mechanism involving communication between several cerebral centers and primitive sacral spinal reflexes. The pudendal nerve is most commonly damaged in females at the level of sacrospinous ligament. We describe the pelvic anatomy and relevant neuroanatomy involved in maintaining urinary continence and during micturition, subsequently highlighting the anatomical basis of urinary incontinence. Comprehensive anatomical understanding is vital for appropriate medical and surgical management of affected patients, and helps guide development of future therapies.

Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury.

UNLABELLED: What's known on the subject? and What does the study add? With the present study, we aimed to provide a global picture of the molecular processes that are activated by CN injury. The present study used genomic expression profiling to identify candidate genes that might be useful targets in the CN recovery process and, thus, the ultimate preservation of penile erection. Regeneration of the CN and axonal outgrowth clearly involve changes in multiple biochemical pathways that have never been investigated by microarray analysis. We analyzed global gene expression in the major pelvic ganglion at early stages (48 h and 14 days) after CN injury and focused on the detection of changes in genes related to nervous tissue repair and proliferation. The findings of the present study provide important insight into the molecular systems affected by CN injury and identify candidate genes that may be utilized for novel molecular-based therapies for the preservation and protection of the CN during RP. OBJECTIVES: To to examine the complexity of the many molecular systems involved in supporting cavernous nerve (CN) repair and regeneration in a rat model of bilateral crush injury utilizing a microarray analysis approach. Erectile dysfunction (ED) is a common clinical complication after prostate cancer treatment by radical prostatectomy, and recovery of erectile function can take as long as 2 years. There are gaps in our understanding of the autonomic pelvic innervation of the penis that still need to be addressed for the development of an adequate treatment strategy for post-prostatectomy ED. The molecular mechanisms of the intrinsic ability of CN to regenerate after an injury have not been elucidated. MATERIALS AND METHODS: We analyzed global gene expression in the major pelvic ganglion 48 h and 14 days after CN injury. Overall, a comparative analysis showed that 325 genes changed at the 48-h time point and 114 genes changed at 14 days. There were 60 changed genes in common with both time points. Using the Ingenuity Pathway Analysis® system (Ingenuity Systems, Inc., Redwood City, CA, USA), we were able to analyze the significantly changed genes that were unique and common to each time point by biological function. We focused on the detection of changes related to nervous tissue repair and proliferation, molecular networks of neurotrophic factors, stem cell regulation and synaptic transmission. RESULTS: There was strong evidence of the early mobilization of genes involved in repair and neuroprotection mechanisms (SERPINF1, IGF1, PLAU/PLAUR, ARG1). Genes related to nervous system development (ATF3 GJA1, PLAU, SERPINE1), nerve regeneration (SERPINE2, IGF1, ATF3, ARG1) and synaptic transmission (GJC1, GAL) were changed. Several genes related to proliferation as well as apoptosis (A2M, ATF3, C3, EGR4, FN1, GJA1, GAL) were also changed, possibly as part of a protective mechanism or the initiation of remodelling. CONCLUSIONS: The results obtained show that multiple biological processes are associated with injury and repair of the CN and provide a systematic genome-wide screen for neurotrophic and/or inhibitory pathways of nerve regeneration. These data identify the candidate genes that may be utilized in novel molecular-based therapies for the preservation and protection of the CN during radical prostatectomy.

Models for sensory neurons of dorsal root ganglia and stress urinary incontinence.

AIMS: To discuss (1) animal models for investigating bladder afferent pathways from the spinal cord to the brain and (2) animal models of stress urinary incontinence (SUI) with a special emphasis on functional and histopathological characteristics of each model. METHODS: Literature review of spinal mechanisms of bladder afferent pathways and animal models of SUI. RESULTS: Electrophysiological studies in the rat using pelvic nerve stimulation and recording of evoked potentials in the periaqueductal gray (PAG) prove to be a valuable tool to examine spinal mechanisms of bladder afferent pathways. Animal models of SUI in the rat include vaginal distention as simulated birth trauma, pudendal nerve crush or transection, urethral sphincter injury by electrocauterization, transabdominal urethrolysis, periurethral botulinum-A toxin injection, and pubo-urethral ligament transection. Functional and histopathological changes in the continence mechanism after injury are different between models. CONCLUSIONS: Using animal models for sensory neurons, intrathecal and intravenous administration of certain drugs can be tested whether they affect the bladder afferent pathways from the spinal cord to the PAG. Animal models of SUI can serve as a tool to develop new pharmacologic therapies or periurethral injection therapies using stem cell implants.

Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury.

The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either vehicle (saline containing bovine serum albumin) or BoNT-A. On day 2, in vitro neurotransmitter release and bladder strip contractility studies as well as in vivo cystometrographic studies were conducted. Resting ATP release was significantly enhanced following spinal cord injury (i.e. 57% increase, p<0.05) and was unaffected by BoNT-A treatment. SCI increased hypoosmotic evoked urothelial ATP release by 377% (p<0.05). BoNT-A treatment reduced evoked ATP release in SCI bladders by 83% (p<0.05). In contrast, hypoosmotic stimulation induced NO release was significantly inhibited following SCI (i.e. 50%, p<0.05) but recovered in SCI rats treated with BoNT-A (i.e. 195% increase in NO release in SCI-BTX-treated rats compared to SCI controls, p<0.01). Changes in urothelial transmitter release coincided with a significant decrease in non-voiding bladder contraction frequency (i.e. 71%, p<0.05) in SCI-BTX rats compared to SCI rats. While no difference was measured between neurally evoked contractile amplitude between SCI and SCI-BTX animals, atropine (1 microM) inhibited contractile amplitude to a greater extent (i.e. 76%, p<0.05) in the SCI-BTX group compared to the SCI group. We hypothesize that alterations in the ratio of excitatory (i.e. ATP) and inhibitory (i.e. NO) urothelial transmitters promote bladder hyperactivity in rat bladders following SCI that can be reversed, to a large extent, by treatment with BoNT-A.

Superior Hypogastric Plexus and Its Surgical Implications During Spine Surgery: A Review.

The superior hypogastric plexus (SHP) is a complex nervous collection located at the lumbosacral region below the level of the aortic bifurcation. As a part of the autonomic nervous system, it is an extension of the preaortic plexuses and continues bilaterally as the hypogastric nerves that ultimately contribute to the inferior hypogastric plexus. Although commonly described as a plexiform structure, several morphologic variations exist. Damage to the SHP can occur during anterior and anterolateral approaches to the lumbosacral spine leading to dysfunction of the abdominopelvic viscera. Visceral afferents travel in the SHP and are responsible for transmitting pain. Management therapies such as SHP blockade or presacral neurectomy can reduce pelvic pain caused by cancer and nonmalignant etiologies. This review highlights some of the recent findings regarding the nature of the SHP.

Urodynamics and bladder muscarinic receptors in rats with cerebral infarction and bladder outlet obstruction.

We characterized muscarinic receptor binding and urodynamic parameters in rats with cerebral infarction and chronic bladder outlet obstruction as models of detrusor overactivity. Bladder weight showed little significant difference between the cerebral-infarcted and sham rats, but the bladder weight was about three times greater in the bladder outlet-obstructed rats. Bladder capacity and voided volume were significantly lower (36.7 and 55.1%, respectively) in the cerebral-infarcted than in the sham rats. Involuntary contractions before micturition were seen in the bladder outlet-obstructed rats but not in sham rats. The bladder outlet-obstructed rats showed significant increases (2.65 and 2.57 times, respectively) in bladder capacity and voided volume, compared with those in sham rats. Bmax values for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the bladder were significantly (34%) increased in the cerebral-infarcted rats compared with sham rats, whereas Kd was unaffected by infarction. On the other hand, there was little significant change in Kd and Bmax for specific [3H]NMS binding in the bladder-obstructed rats compared with sham rats. In conclusion, the present study shows that cerebral infarction but not bladder outlet obstruction in rats causes up-regulation of bladder muscarinic receptors, and that such regulation of bladder muscarinic receptors may be at least partly associated with the symptoms of detrusor overactivity subsequent to cerebral infarction.

Possible role of the major pelvic ganglion in the modulation of non-voiding activity in rats.

AIMS: The existence of a motor-sensory system contributing to bladder sensation is now becoming widely accepted. Although it is clear that the motor component of this system appears to be generated within the bladder wall, recent observations suggest that the mechanisms involved in its modulation may lie outside the wall. The present study was undertaken to gain more insights into the peripheral modulation of non-voiding activity and the role of the major pelvic ganglion. METHODS: Male Sprague-Dawley rats anesthetized with urethane were used. The bladder was filled till 60% of the micturition threshold volume. The baseline pressure and the superimposed non-voiding activity were observed before and after consecutive bilateral transections of the hypogastric and pelvic nerves and bilateral ablation of the major pelvic ganglia. RESULTS: Hypogastric and pelvic nerve transection didn't significantly change the baseline pressure and superimposed non-voiding activity. Removal of the major pelvic ganglia resulted into an increased baseline pressure when compared with the control and increased amplitude of the non-voiding contractions when compared with both the decentralized condition (both hypogastric and pelvic nerves transected) and the control. The frequency of the non-voiding contractions wasn't affected. CONCLUSIONS: Non-voiding activity during the urine storage phase seems to be modulated at the level of the major pelvic ganglion. This suggests the possibility of local circuits between the bladder and the peripheral ganglia that may be responsible for an inhibitory component influencing non-voiding activity.

Current concepts and practical techniques of nerve-sparing laparoscopic radical hysterectomy.

Laparoscopic radical hysterectomy has been widely performed for patients with early-stage cervical cancer. The operative techniques for nerve-sparing to avoid bladder dysfunction have been established during the past three decades in abdominal radical hysterectomy, but how these techniques can be applied to laparoscopic surgery has not been fully discussed. Prolonged operation time or decreased radicality due to less accessibility via a limited number of trocars may be a disadvantage of the laparoscopic approach, but the magnified visual field in laparoscopy may enable fine manipulation, especially for preserving autonomic nerve tracts. The present review article introduces the practical techniques for sparing bladder branches of pelvic nerves in laparoscopic radical hysterectomy based on understanding of the pelvic anatomy, clearly focusing on the differences from the techniques in abdominal hysterectomy.

A spinal cord injured animal model of lower urinary tract function: observations using direct bladder and pelvic plexus stimulation with model microstimulators.

BACKGROUND: Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume. METHODS: In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling. RESULTS: The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed. CONCLUSIONS: This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.

Chronic instrumentation with model microstimulators in an animal model of the lower urinary tract.

BACKGROUND: Microstimulators are a new type of neuroprosthetic device that should be considered for applications such as micturition control after spinal cord injury (SCI). These devices are small (less than 25 mm by 5 mm) and the electrodes are located on the ends of the stimulator. The aim of the current study was to develop methods for chronic implantation of model microstimulators (M-Micro) on the bladder wall and pelvic plexus of female cats. A postmortem evaluation of the effects of 3 months of implantation is reported. METHODS: Techniques to produce the M-Micro are described. Four of these devices were implanted in 4 female cats and maintained after the initial instrumentation surgery and a second survival surgery for SCI (at T10). Using a single suture tied around the M-Micro, these devices were secured to the bladder wall or the fat pads adjacent to the pelvic plexus. Additional instrumentation was implanted, including 2 catheters in the bladder, 1 abdominal balloon, and electromyography electrodes in the urethral and anal sphincters. Postmortem observations of the location of the M-Micro on the bladder wall were conducted after fixation. RESULTS: The animals' conditions were good. One animal was sacrificed early because of a skin infection. A single suture was sufficient to anchor the M-Micro. However, during the surgical implantation the pelvic plexus M-Micro ended up close to the bladder neck. Extensive fibrous connective tissue formed around the M-Micro and implanted catheters on the bladder wall. This appeared to result, in part, from multiple devices implanted on or near the bladder wall. CONCLUSIONS: These pilot studies showed that the M-Micro could be easily constructed and secured to the bladder wall or fat pads close to the pelvic plexus. There was a concern that the pelvic plexus location for the M-Micro ended near the bladder neck during the surgical implantation; however, these devices did not appear to migrate over this short, 3-month implantation period. The extensive connective tissue responses of the bladder wall to the tubes, wires, and M-Micro was a major concern. The M-Micro appears to be a good device to assess the potential of commercial microstimulators for use in micturition control.

Inferior hypogastric plexus blockade versus acupuncture for the management of idiopathic chronic pelvic pain: A randomized clinical trial.

BACKGROUND: To compare the clinical efficacies of inferior hypogastric plexus blockade and acupuncture in the management of idiopathic chronic pelvic pain (CPP). METHODS: The study included 117 patients with CPP. Group 1 included 62 patients who underwent inferior hypogastric plexus blockade and group 2 included 55 patients who underwent acupuncture. Pain level was assessed using a visual analogue scale (VAS) immediately and at 2, 6, and 12 weeks after treatment. RESULTS: The preprocedure VAS score was 7.6 ± 0.15 in group 1 and 7.7 ± 0.24 in group 2 (p > 0.05). Pelvic pain decreased significantly in both groups after treatment, with pretreatment and posttreatment scores of 7.6 ± 0.15 and 2.2 ± 0.88, respectively, in group 1 (p < 0.0001) and 7.7 ± 0.24 and 4.7 ± 0.11, respectively, in group 2 (p < 0.0001). However, the decrease in pain scores throughout the clinical follow-up was significantly more in group 1 than in group 2 (p< 0.0001). Complete disappearance of symptoms was achieved in 72.6% of patients in group 1 compared to 54.5% of patients in group 2 (p = 0.3737). Patients who did not benefit from the treatment were significantly more in group 2 than in group 1 (25.5% vs. 6.5%, p = 0.0294). No complications were reported in both groups. CONCLUSION: The study results showed that inferior hypogastric blockade had a 72.6% success rate and showed a significantly higher effect on reducing pain intensity in a short period of time in the management of CPP, compared to acupuncture.

Preservation of the neurovascular bundles is associated with improved time to continence after radical prostatectomy but not long-term continence rates: results of a systematic review and meta-analysis.

CONTEXT: The aetiology of urinary incontinence following radical prostatectomy (RP) is incompletely understood. In particular, it is unclear whether there is a relationship between neurovascular bundle (NVB) sparing and post-RP urinary continence. OBJECTIVE: To review systematically the association of NVB sparing in RP with postoperative urinary continence outcomes and synthesise the results in a meta-analysis. EVIDENCE ACQUISITION: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. PubMed, Medline, and Cochrane Central Register of Controlled Trials were searched (December 2013), yielding 3413 unique records. A total of 27 longitudinal cohort studies were selected for inclusion. Studies were evaluated using a predefined criteria adapted from the Cochrane Tool to Assess Risk of Bias in Cohort Studies. EVIDENCE SYNTHESIS: Data from 13 749 participants in 27 studies were synthesised in a meta-analysis. An assessment of the study methodology revealed a high risk of bias due to differences in baseline characteristics, outcome assessment, and the likely presence of unreported confounding factors such as meticulous apical dissection. Meta-analysis demonstrated that nerve sparing (NS) compared with non-nerve sparing (NNS) resulted in improved early urinary continence rates up to 6 mo postoperatively. Beyond this time, no significant difference was observed. This effect was seen most clearly for bilateral NS compared with NNS. A sensitivity analysis of prospective cohort studies revealed consistent results. CONCLUSIONS: This analysis demonstrates an association between NS and improved urinary continence outcomes up to 6 mo postoperatively. NS in men with poor preoperative erectile function should be considered in the context of oncologic risk stratification because it may improve time to continence recovery. The underlying cause of the relationship between NS and continence is unknown. It may represent preservation of the intrapelvic somatic nerves supplying the rhabdosphincter or the influence of other confounding factors. Future research should be directed towards improving understanding of the anatomy of urinary continence and the pathophysiology of post-RP incontinence. PATIENT SUMMARY: We found that avoiding damage to the nerves around the prostate improves urinary continence in the first 6 mo after surgery. After this time, there is no difference in continence between men who had these nerves removed and those who had them saved. This finding could be due to a true effect of saving these nerves or to a number of other factors affecting the research.

Colokinetic effect of noradrenaline in the spinal defecation center: implication for motility disorders.

Chronic abdominal pain in irritable bowel syndrome (IBS) usually appears in combination with disturbed bowel habits, but the etiological relationship between these symptoms remains unclear. Noradrenaline is a major neurotransmitter controlling pain sensation in the spinal cord. To test the hypothesis that the descending noradrenergic pathway from the brain stem moderates gut motility, we examined effects of intrathecal application of noradrenaline to the spinal defecation center on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anesthetized rats. Intrathecal application of noradrenaline into the L6-S1 spinal cord, where the lumbosacral defecation center is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons by tetrodotoxin blocked the effect of noradrenaline. Pharmacological experiments showed that the effect of noradrenaline is mediated primarily by alpha-1 adrenoceptors. The enhancement of colorectal motility by intrathecal noradrenaline was abolished by severing of the pelvic nerves. Our results demonstrate that noradrenaline acting on sacral parasympathetic preganglionic neurons through alpha-1 adrenoceptors causes propulsive motility of the colorectum in rats. Considering that visceral pain activates the descending inhibitory pathways including noradrenergic neurons, our results provide a rational explanation of the concurrent appearance of chronic abdominal pain and colonic motility disorders in IBS patients.

Responses of neurons in nucleus ventralis posterolateralis of the cat thalamus' to hypogastric inputs.

Recordings were made from 68 units in the nucleus ventralis posterolateralis (VPL) of the cat thalamus, which responded to stimulation of hypogastric afferents. These units also received nociceptive inputs from the contralateral integument. Units which responded exclusively to hypogastric afferent inputs were not found. Thirty seven of the units were nociceptive specific (NS), and the remaining 31 were wide dynamic range (WDR) units. All of these units were located in the shell region of the lateral subdivision of the caudal VPL. NS units responding to hypogastric afferent inputs had a circumscribed cutaneous receptive field on the contralateral abdomen, gluteal region, tail or hind limb. These areas corresponded to tactile dermatomes T13-S2. Similarly, the cutaneous receptive fields of WDR units receiving hypogastric afferent inputs were distributed in the contralateral abdomen, gluteal region, tail and hind limb, with the sole exception of one unit, whose receptive field also included a part of the lower thorax. These findings extend the previous findings that the shell region of the caudal VPL of the cat thalamus constitutes a thalamic link in a visceral pain pathway, and that the visceral and cutaneous pathways share a common projection locus in the VPL.

Responses of rat spinal neurones to natural and electrical stimulation of colonic afferents: effect of inflammation.

Single unit electrical activity has been recorded from 107 neurones excited by electrical stimulation of the pelvic nerve in or around lamina X of the L6-S1 spinal cord in anaesthetised rats. Responses to colorectal distension (CRD; 30 s, 5-80 mmHg) and to somatic electrical and mechanical stimulation were characterised. Of 107 neurones excited by pelvic nerve stimulation, 58 (54%) were affected by CRD: 46 neurones were excited (39 with a sustained response and 7 with an on-off response) and 12 neurones were inhibited. The vast majority of the neurones affected by CRD (54/58) had nociceptive somatic receptive fields. Neurones excited by CRD showed graded stimulus response functions in the noxious range (20-80 mmHg), except for two neurones which only encoded stimulus intensity below 20 mmHg. Neurones inhibited by CRD had significantly larger somatic receptive fields, and more superficial recording sites than those excited by CRD. A group of 12 neurones with sustained excitatory responses to CRD were characterised before and 45 min after intracolonic instillation of 1 ml 0.6% acetic acid. Colon inflammation provoked a significant increase in responses to CRD and to pelvic nerve stimulation (n=12), but no significant change in responses to pinch of their somatic receptive field (n=10). We conclude that of these neurones, the population with excitatory sustained responses to CRD are those likely responsible for processing information leading to acute pain sensations from the colon, and also show central sensitisation after colon inflammation, suggesting they play an important role in development of colonic hyperalgesia.

Cavernous nerve injury elicits GAP-43 mRNA expression but not regeneration of injured pelvic ganglion neurons.

Recovery of erectile dysfunction after cavernous nerve injury takes a long period. To elucidate this mechanism, unilateral cavernous nerve of male rat was cut, and the expression level of a nerve regeneration marker, the growth associated protein-43 (GAP-43) mRNA was evaluated by in situ hybridization and RT-PCR. While GAP-43 mRNA expression was transiently increased in the injured neurons of the major pelvic ganglion (MPG) at 7 days after nerve injury, continuous increase of GAP-43 mRNA was observed in the contralateral MPG from 7 days to 6 months after the nerve injury. Histochemical double-labeling studies for either neuronal NOS (nNOS) or tyrosine hydroxylase (TH) and the GAP-43 mRNA expression demonstrated that in injured MPG the transient up-regulation of GAP-43 mRNA was mainly seen in nNOS negative and/or TH positive neurons, suggesting non-parasympathetic post-ganglionic neurons, and also demonstrated that in contralateral MPG GAP-43 mRNA positive neurons were gradually increased in nNOS positive but TH negative neurons, suggesting parasympathetic post-ganglionic neurons. When a retrograde tracer Fluorogold (FG) was injected into the penile crus 7 days before histological experiments, FG-positive neurons were, if any, hardly seen in nNOS-positive neurons of the injured MPG for at least 6 months, whereas numerous FG-positive cells were seen in nNOS-positive neurons of the contralateral MPG. These results suggest that post-ganglionic projecting neurons of the intact side, which express increased GAP-43 mRNA, would be most likely to contribute to the recovery of the erectile function after unilateral cavernous nerve injury possibly by a plastic change such as nerve sprouting.