Transecting the hypogastric nerve to uncover the bladder-inhibitory pathways involved with saphenous nerve stimulation in anesthetized rats.

Saphenous (SAFN) nerve stimulation was recently shown in anesthetized rats to elicit bladder-inhibitory responses in a frequency-dependent manner; however, the mechanism of action is unknown. The goal of this study was to investigate the potential role of the hypogastric nerve (HGN) in this inhibitory pathway by examining stimulation-evoked changes in bladder function under four different experimental conditions: (1) HGN intact, saline infusion (HGNi-s), (2) HGN transected, saline infusion (HGNt-s), (3) HGN intact, acetic acid (AA) infusion (HGNi-a), and (4) HGN transected, AA infusion (HGNt-a). Experiments were conducted in 33 urethane-anesthetized female rats, where continuous bladder infusion was provided through a suprapubic catheter. The experimental protocol involved two, 40-min stimulation trials in which electrical pulses were applied to the SAFN at a set frequency (10 Hz) and two different amplitudes (50 µA and 100 µA). In all experimental groups, SAFN stimulation resulted in complete suppression of bladder activity with an incidence rate of 25% to 50%. However, significant changes in the measured urodynamic changes (e.g., basal pressure, contraction amplitude, and inter-contraction interval) were found only in the HGNt-a animals. Our findings suggest that the HGN does not mediate the inhibitory effects of SAFN stimulation and that bladder inhibition is achieved through a different mechanism of action.

Response of hypogastric afferent fibers to bladder distention or irritation in cats.

The goal of this study in anesthetized cats was to identify silent hypogastric nerve (HGN) afferent fibers that do not respond to bladder distention but become responsive after chemical irritation of the bladder. The HGN was split into multiple filaments small enough for recording action potentials from single or multiple afferent fibers. The bladder was distended by infusion of either saline or 0.5% acetic acid (AA) through a urethral catheter while recording intravesical pressure. A total of 90 HGN filaments from 17 cats responded to bladder distention with saline or AA. Three types of HGN afferents were identified. The first type was non-nociceptive mechano-sensitive that responded to bladder distention at normal physiological pressures (10-40 cmH2O). The second type was nociceptive mechano-sensitive that only responded to high-pressure (50-80 cmH2O) bladder distention with saline but responded to low-pressure bladder distention after sensitization with AA. The third type was chemo-sensitive nociceptive that was silent even during high-pressure bladder distention but after sensitization with AA did respond to low-pressure bladder distention. These results indicate that HGN afferents as well as pelvic nerve afferents may play a role in bladder nociception. The HGN afferent fibers that are silent during bladder distention at normal physiological pressures but become responsive after chemical irritation are important for understanding the possible pathophysiological mechanism underlying bladder allodynia in painful bladder syndrome.

Pulsed Radiofrequency of the Sacral Roots Improves the Success Rate of Superior Hypogastric Plexus Neurolysis in Controlling Pelvic and Perineal Cancer Pain.

BACKGROUND: Superior hypogastric plexus neurolytic (SHP-N) block is the mainstay management for pelvic cancer pain of visceral origin when oral opioids fail due to inefficacy or intolerance to side effects. Unfortunately, SHP-N has the potential to control pelvic pain in 62%-72% of patients at best, because chronic pelvic pain may assume additional characteristics other than visceral. OBJECTIVE: Combining SHP-N with pulsed radiofrequency (PRF) of the sacral roots might block most of the pain characteristics emanating from the pelvic structures and improve the success rate of SHP-N in controlling pelvic and perineal cancer pain. STUDY DESIGN: This study was a prospective randomized controlled clinical trial. SETTINGS: The research took place in the interventional pain unit of a tertiary center in the university hospital. METHODS: Fifty-eight patients complaining of cancer-related chronic pelvic and perineal pain were randomized to either the PRF + SHP group (n = 29), which received SHP-N combined with PRF of the sacral roots S2-4, or the SHP group (n = 29), which received SHP-N alone. The outcome variables were the percentage of patients who showed a > 50% reduction in their Visual Analog Scale (VAS) pain score, the VAS pain score, and global perceived effect evaluated during a 3-month follow-up period. RESULTS: The percentage of patients who showed a > 50% reduction in their VAS pain score was significantly higher in the SHP + PRF group compared to the SHP group when assessed at one month (92.9% [n = 26] vs 57.7% [n = 15]; P = .003) and 3 months (85.7% [n = 24) vs 53.8% [n = 14]; P = .01) post procedure, respectively. However, no significant difference was observed between the 2 groups at the 6-month evaluation (SHP + PRF [57.1% (n = 16)] vs SHP [50% (n = 13)]; P = .59). There was a statistically significant reduction of VAS in the SHP + PRF group in comparison to the SHP group at one month (2.8 ± 0.9 vs 3.5 ± 1.2 [mean difference, -0.7 (95% confidence interval [CI], -1.29 to -0.1), P = .01]), 2 months (2.8 ± 0.9 vs 3.5 ± 1.2 [mean difference, -0.64 (95% CI, -1.23 to -0.05), P = .03]), and 3 months (2.7 ± 1 vs 3.4 ± 1.2 [mean difference, -0.67 (95% CI, -1.29 to -0.05)], P = .03]) post procedure, respectively; however, the 2 groups did not significantly differ at 2 weeks, 4, 5, and 6 months post procedure. Regarding postprocedural analgesic consumption, there were trends towards reduced opioid consumption at all postprocedural measured time points in the SHP+PRF group compared to the SHP group; these differences reached statistical significance at 2 months (median, 30 [interquartile range (IQR), 0.00-30] vs median, 45 [IQR, 30-90]; P = .046) and 3 months (median, 0.00 [IQR, 0.00-30] vs median, 30 [IQR, 0.00-67.5]; P = .016) post procedure, respectively. LIMITATIONS: The study follow-up period is limited to 6 months only. CONCLUSIONS: SHP-N combined with PRF of the sacral roots (S2, 3, 4) provided a better analgesic effect than SHP-N alone for patients with chronic pelvic and perineal pain related to pelvic cancer. TRIAL REGISTRY: ClinicalTrials.gov. NCT03228316. KEY WORDS: Pelvic pain, pulsed radiofrequency, sacral roots, superior hypogastric plexus.

Effectiveness of Superior Hypogastric Plexus Neurolysis for Pelvic Cancer Pain.

BACKGROUND: The superior hypogastric plexus block has been indicated for visceral pelvic pain treatment associated with malignancy. The first international report of this technique was published by Plancarte et al, in which a posterior percutaneous approach guided by fluoroscopy was described by applying neurolytic agents. The considerable variability in the data reported gave rise to 2 clinical approaches to those who performed the blockade early and those who executed it at a later stage of cancer. OBJECTIVES: The present study aims to provide more evidence regarding the effectiveness of this procedure. STUDY DESIGN: This is a retrospective, longitudinal, descriptive study. SETTING: The study was held at the pain unit service of the National Cancer Institute, Mexico City. METHODS: A nonprobabilistic sample was selected; the data collection took place from January 2006 to December 2016 with patients diagnosed with pelvic pain, confirmed by imaging and biopsy studies. Patients who received any other type of intervention of the sympathetic axis, patients with a different approach than the classic or paravertebral technique, and patients with low survival rate were excluded. The Student t test was used to measure the significant difference between Visual Analog Scale (VAS) and morphine equivalent daily dose. The Cochran-Mantel-Haenszel test and the Gamma test were used to measure the association between the initial Karnofsky and blockade success. RESULTS: The study included a total of 180 patients. The success rate was 59.4% at 1 month, 55.5% at 3 months, and 48.8% at 6 months. There was a sustained and significant VAS reduction that was 49.55% at 3 months. A significant reduction in opioid consumption of 12.55% was found at 3 months. There was no significant statistical evidence related to either opioid consumption or the functionality of the patient before the blockade as an influential variable in the success of the procedure. LIMITATIONS: Retrospective study, developed in a single center. CONCLUSIONS: Although opioids remain the cornerstone of cancer pain treatment, they produce many deleterious side effects. The superior hypogastric plexus neurolysis represents a reproducible and effective alternative in the management of pain in this group of patients. KEY WORDS: Pelvic pain, neoplasms, chemical neurolysis, pain management, cancer pain, palliative care, analgesia, nerve block.

The expression of androgen receptor in neurons of the anterior pelvic ganglion and celiac-superior mesenteric ganglion in the male pig.

The present study investigated the expression of androgen receptor (AR) in neurons of the anterior pelvic ganglion (APG) and celiac-superior mesenteric ganglion (CSMG; ganglion not involved in the innervation of reproductive organs) in the male pig with quantitative real-time PCR (qPCR) and immunohistochemistry. qPCR investigations revealed that the level of AR gene expression in the APG tissue was approximately 2.5 times higher in the adult (180-day-old) than in the juvenile (7-day-old) boars. Furthermore, in both the adult and juvenile animals it was sig- nificantly higher in the APG than in CSMG tissue (42 and 85 times higher, respectively). Immu- nofluorescence results fully confirmed those obtained with qPCR. In the adult boars, nearly all adrenergic (DßH-positive) and the majority of non-adrenergic neurons in APG stained for AR. In the juvenile animals, about half of the adrenergic and non-adrenergic neurons were AR-posi- tive. In both the adult and juvenile animals, only solitary CSMG neurons stained for AR. The present results suggest that in the male pig, pelvic neurons should be considered as an element of highly testosterone-dependent autonomic circuits involved in the regulation of urogenital func- tion, and that their sensitization to androgens is a dynamic process, increasing during the prepu- bertal period.

Urethral regions with differential tissular composition may underlie urinary continence and voiding function in female rats.

AIMS: To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. METHODS: Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. RESULTS: The female rat urethra is not a homogeneous tubular organ. The pre-pelvic and pelvic regions are firmly attached to the vagina with belt-like striated fibers forming a urethra-vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra-clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). CONCLUSIONS: Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra-vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra-clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.

Sonic hedgehog regulation of cavernous nerve regeneration and neurite formation in aged pelvic plexus.

INTRODUCTION: Erectile dysfunction (ED) is a significant health concern that greatly impacts quality of life, and is common in men as they age, impacting 52% of men between the ages of 40 and 70. A significant underlying cause of ED development is injury to the cavernous nerve (CN), a peripheral nerve that innervates the penis. CN injury also occurs in up to 82% of prostatectomy patients. We recently showed that Sonic hedgehog (SHH) protein delivered by peptide amphiphile (PA) nanofiber hydrogel to the CN and penis of a prostatectomy model of CN injury, is neuroprotective, accelerates CN regeneration, improves erectile function ~60%, preserves penile smooth muscle 56% and suppresses collagen deposition 30%. This regenerative potential is substantial in an adult prostatectomy model (P120). However prostatectomy patients are typically older (61.5 ±â€¯9.6 years) and our models should mimic patient conditions more effectively when considering translation. In this study we examine regenerative potential in an aged prostatectomy model (P200-329). METHODS: The caudal portion of the pelvic ganglia (MPG) and CN were dissected from adult (n = 11), and aged (n = 13) Sprague Dawley rats, and were grown in organ culture 3 days. Uninjured and 2 day CN crushed MPG/CN were exposed to Affi-Gel beads containing SHH protein, PBS (control), or 5e1 SHH inhibitor. Neurites were quantified by counting the number of growth cones normalized by tissue perimeter (mm) and immunohistochemistry for SHH, patched1 (PTCH1), smoothened (SMO), GLI1-3, and GAP43 were performed. RESULTS: SHH treatment increased neurites 3.5-fold, in uninjured adult, and 5.7-fold in aged rats. Two days after CN crush, SHH treatment increased neurites 1.8-fold in adult rats and 2.5-fold in aged rats. SHH inhibition inhibited neurite formation in uninjured MPG/CN but not in 2 day CN crushed MPG/CN. PTCH1 and SMO (SHH receptors), and SHH transcriptional activators/repressors, GLI1-3, were abundant in aged MPG/CN with unaltered localization. ROCK1 was induced with SHH treatment. CONCLUSIONS: Reintroduction of SHH protein in an aged prostatectomy model is even more effective in promoting neurite formation/CN regeneration than in the adult. The first 48 h after CN injury are a critical window when growth factors are released, that impact later neurite formation. These studies are significant because most prostatectomy patients are not young and healthy, as with adult rats, so the aged prostatectomy model will more accurately simulate ED patient response. Understanding how neurite formation changes with age is critical for clinical translation of SHH PA to prostatectomy patients.

Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT1A receptors in controlling the UFR in female rats.

Laparoscopically implanted system for stimulation of the hypogastric plexus induces colonic motility, defecation, and micturition: experimental study.

BACKGROUND: Modulation of the enteric nervous system seems to be promising in several functional colorectal disorders for which targeted, causal treatment methods do not exist. However, sacral nerve stimulation can induce undesirable muscle contraction or paresthesia. Therefore, we have developed a laparoscopic technique for implanting a neural electrode, placed directly over the pelvic autonomic nerve plexus. The aim of this experimental study was to evaluate the effect of stimulating the hypogastric plexus and pelvic nerves on inducing distal colon contraction, defecation, and micturition. METHOD: A total of 10 white, male healthy pigs (25-30 kg) were subjected to the laparoscopic implantation of the electrode and the stimulator. In the third and fourth weeks postimplantation, the efficacy of the acute and chronic stimulation to induce defecation was evaluated. RESULTS: The average operative time was 105 minutes (85-150 minutes). In all pigs, acute stimulation activated induced defecation, every second day, every time on demand, with an average delay of 139.7 s. Micturition was induced incidentally. Acute or chronic stimulation did not cause any harm, pain, or suffering to the animals. No adverse effects of the stimulation were observed, and no septic complications or macroscopic fibrosis around the electrodes were found on autopsy. CONCLUSION: Hypogastric plexus stimulation can be a useful and safe option of distal colon contraction, defecation, and micturition. However, the efficacy of the stimulation was observed for a relatively short period of time, and it is not known if it will be sustained for a longer duration.

Is pelvic plexus nerve documentation feasible during robotic assisted laparoscopic ureteral reimplantation with extravesical approach?

PURPOSE: Urinary retention is a known complication of using an extravesical approach for ureteral reimplantation, especially in bilateral cases. The etiology may be secondary damage to pelvic nerves during ureteral dissection. Recent literature suggests that it is possible to visually identify these nerves during a robotic assisted laparoscopic approach. We performed an exploratory study to identify and document them in pediatric patients by means of electrophysiologic recordings. MATERIAL AND METHODS: Seven consecutive patients undergoing robotic assisted laparoscopic ureteral reimplantation with extravesical approach were prospectively enrolled in the study. Following dissection of the ureter below the level of vas deferens in male and the uterine artery in female, staying close to the adventitia and approaching the ureterovesical junction, the fibers as described in human cadaveric studies were identified dorsomedial to the ureter and preserved. Stimulating and recording electrodes were passed through to record post-synaptic compound muscle action potentials of the bladder. RESULTS: Even though the nerve fibers were visually identified, we were unable to consistently and reproducibly record compound muscle action potentials after stimulation of putative pelvic plexus fibers at the distal ureter, despite modulation in stimulation intensity, pulse characteristics, signal recording sensitivity and stimulator probe variation. CONCLUSIONS: In this pilot study, the inconsistent findings raise questions about the exact location of the neurovascular bundle, nature of bladder smooth muscle electrophysiology and the appropriate methodology of evaluation. This may provide a reason to reexamine the intraoperatively expected location of pelvic plexus nerve fibers.

Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia.

The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

Afferent signaling from the bladder: species differences evident from extracellular recordings of pelvic and hypogastric nerves.

The afferent nervous system plays an important role in the regulation of lower urinary tract (LUT) function. Multiple methods to study the afferent nervous system in the LUT have been described. This overview focuses on extracellular afferent nerve recordings of the pelvic and hypogastric nerves in cat, rat, mouse, and guinea pig from in vivo and in vitro models and considers how such recordings may lend to the understanding of interspecies differences.

Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K+ channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder and colon.

The bladder and distal colon are innervated by lumbar splanchnic (LSN) and pelvic nerves (PN) whose axons arise from dorsal root ganglia (DRG) neurons at thoracolumbar (TL) and lumbosacral (LS) spinal levels, respectively. In an attempt to understand the molecular basis of differences between LSN and PN mechanosensitive afferents, we analyzed the gene expression of two potentially counteracting ion channel groups involved in mechanosensation, transient receptor potential channels (TRPV1 and TRPA1) and mechanosensitive two pore-domain K(+) (K(2P)) channels (TREK-1, TREK-2 and TRAAK), in TL and LS DRG neurons innervating mouse bladder or distal colon. The proportion of TRPV1-expressing cells (41∼61%) did not differ between TL and LS neurons innervating bladder or colon. TRPA1 was seldom detected in bladder LS neurons whereas it was expressed in 64∼66% of bladder TL, colon TL and colon LS neurons. Coexpression of TRPV1 and TRPA1 was frequent. TREK-1-expressing cells were more prevalent in LS than TL ganglia in both bladder- and colon-DRG neurons. All three K(2P) channels were detected more frequently in TRPV1-positive neurons in TL ganglia. More than half of TL neurons expressing only TRPA1 were devoid of any of the three K(2P) channels, whereas all TL neurons expressing both TRPA1 and TRPV1 expressed at least one of the K(2P) channels. These results reveal clear differences between LSN and PN sensory pathways in TRPA1 and TREK-1 gene expression and in the gene expression of K(2P) channels in TRPV1-expressing neurons. This study further documents heterogeneity of visceral afferents based on combinations of the five channels examined.

Regeneration and functional recovery of intrapelvic nerves removed during extensive surgery by a new artificial nerve conduit: a breakthrough to radical operation for locally advanced and recurrent rectal cancers.

PURPOSE: In the current strategy against locally advanced and recurrent rectal cancers possibly involving intrapelvic nerves, there has been a serious dilemma between extensive surgery and limited surgery. The former can attain high tumor curability by sacrificing the nerve functions while the latter prioritizes the patient quality of life by preserving the nerve functions but with a compromised curability. Here we present a new surgical strategy for locally advanced and recurrent rectal cancers, which realize both high tumor curability and good quality of life. METHODS: A new artificial nerve conduit (polyglycolic acid collagen tube) developed by in site tissue engineering technology was applied to recovery the disturbed functions after removing the nerves from 11 patients undergoing extensive surgery for intrapelvic advanced or recurrent colorectal cancers. The reconstructed nerves included eight autonomic nerves which are essential for the genitourinary function and three somatic nerves which control the sensation and mobility of the legs. RESULTS: Out of ten cases followed up more than 2 years and evaluated fully, eight including two report cases showed a functional recovery of the disturbed autonomic and somatic nerves clinically. The nerve function started to recover from 3 to 6 months after the operation and continued to improve with times. No specific complications associated with the nerve repair have been noted. CONCLUSIONS: The new strategy utilizing the nerve conduit can be a breakthrough in radical operations for locally advanced and recurrent rectal cancers to resolve the problems between tumor curability and the patient quality of life.

Mechanisms of reflex bladder activation by pudendal afferents.

Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a ß-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by -25% to -39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder contractions following administration of hexamethonium bromide confirmed that contractions were generated by pelvic efferent activation via the pelvic ganglion. These findings indicate that pudendal afferent stimulation evokes bladder contractions through convergence with pelvic afferents to increase pelvic efferent activity.

Effects of autonomic nerve stimulation on colorectal motility in rats.

BACKGROUND: Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats. METHODS: Four strain gauge transducers were implanted on the proximal colon, mid colon, distal colon and rectum to record circular muscle contractions in rats. Electrical stimulation was administered to the efferent distal ends of the cervical vagus nerve, PN and HGN. Motility index (MI) was evaluated before and during stimulation. KEY RESULTS: Electrical stimulation (5-20 Hz) of the cervical vagus elicited significant contractions in the mid colon and distal colon, whereas less pronounced contractions were observed in the proximal colon. Pelvic nerves stimulation elicited significant contractions in the rectum as well as the mid colon and distal colon. Atropine treatment almost completely abolished the contractions induced by vagus nerve and PN stimulation. Hypogastric nerves stimulation caused relaxations in the rectum, mid colon and distal colon. The relaxations in response to HGN stimulation were abolished by propranolol. CONCLUSIONS & INFERENCES: Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors.

Striated perineal muscles: location of autonomic, sensory, and somatic neurons projecting to the male pig bulbospongiosus muscle.

The location, number, and size of the neurons innervating the bulbospongiosus muscle (BSM) were studied in male pigs, by means of Fast Blue (FB) retrograde transport. After injection of FB into the left BSM, labeled neurons were found bilaterally in the L2-S4 sympathetic trunk ganglia (STGs), in the caudal mesenteric ganglia (CMGs), in the microganglia of the pelvic plexus (PGs), in a dorsolateral area with respect to the central canal of S1-S3 segments of the spinal cord (SC) and in the S1-S4 ipsilateral and S2-S3 contralateral spinal ganglia (SGs). The mean number of labeled FB cells was 3,122 +/- 1,968 in STGs, 979 +/- 667 in CMGs, 108 +/- 104 in PGs, 89 +/- 39 in SC and 77 +/- 23 in SGs. The area of the multipolar neurons was 852 +/- 22 microm(2) in the STGs, 878 +/- 23 microm(2) in the CMGs and 922 +/- 31 microm(2) in the PGs. The multipolar SC neurons had an area of 1,057 +/- 38 microm(2), while pseudounipolar SG cells had dimensions of 2,281 +/- 129 microm(2). Our research enables us to highlight two peculiarities regarding the innervation of the boar BSM: the very high number of labeled autonomic neurons and the particular localization of the motor somatic nucleus.

Sympathetic and parasympathetic regulation of rectal motility in rats.

INTRODUCTION: The colon and rectum are regulated by the autonomic nervous system (ANS). Abnormalities of the ANS are associated with diseases of the colon and rectum while its modulation is a putative mechanism for sacral nerve stimulation. The purpose of this study is to establish a rat model elucidating the role of the efferent ANS on rectal motility. MATERIALS AND METHODS: Rectal motility following transection or stimulation of parasympathetic pelvic nerves (PN) or sympathetic hypogastric nerves (HGN) was measured with rectal strain gauge transducers and quantified as a motility index (MI). Colonic transit was measured 24 hours after transection by calculating the geometric center (GC) of distribution of (51)Cr RESULTS AND DISCUSSION: Transection of PN and HGN decreased MI to 518 +/- 185 g*s (p < 0.05) and increased MI to 5,029 +/- 1,954 g*s (p < 0.05), respectively, compared to sham (975 +/- 243 g*s). Sectioning of PN and HGN decreased transit with GC = 4.9 +/- 0.2 (p < 0.05) and increased transit with GC = 8.1 +/- 0.7 (p < 0.02), respectively, compared to sham (GC = 5.8 +/- 0.3). Stimulation of PN and HGN increased MI to 831 +/- 157% (p < 0.01) and decreased MI to 251 +/- 24% (p < 0.05), respectively. CONCLUSION: Rectal motility is significantly altered by sectioning or stimulating either HGN or PN. This model may be useful in studying how sacral nerve stimulation exerts its effects and provide insight into the maladies of colonic motility.

Mechanisms of adaptive supersensitivity in vas deferens.

Adaptive supersensitivity is a phenomenon characteristic of excitable tissues and discloses as a compensatory adjustment of tissue's response to unrelated stimulatory endogenous and exogenous substances after chronic interruption of excitatory neurotransmission. The mechanisms underlying such higher postjunctional sensitivity have been postulated for a variety of cell types. In smooth muscles, especially the vas deferens with its rich sympathetic innervation, the mechanisms responsible for supersensitivity are partly understood and appear to be different from one species to another. The present review provides a general understanding of adaptive supersensitivity and emphasizes early and recent information about the putative mechanisms involved in this phenomenon in rodent vas deferens.

Cervix remodeling and parturition in the rat: lack of a role for hypogastric innervation.

The hypogastric nerve is a major pathway innervating the uterine cervix, yet its contribution to the processes of cervical ripening and parturition is not known. The main objective of this study was to determine the effect of hypogastric nerve transection on remodeling of the cervix and timing of birth. As an initial goal, processes associated with remodeling of the peripartum cervix were studied. The cervix was obtained from time-dated pregnant rats on days 15, 19, 21, and 21.5 of pregnancy, and post partum on the day of birth (day 22). The cervix was excised, post-fixed overnight, and sections stained to evaluate collagen content and structure or processed by immunohistochemistry to identify macrophages or nerve fibers. The census of macrophages and density of nerve fibers in the cervix peaked on day 21, the day before birth, and then declined post partum. These results replicate in time course and magnitude previous studies in mice. To address the main objective, the hypogastric nerve was bilaterally transected on day 15 post-breeding; sham-operated rats served as controls. Pups were born in both groups at normal term. Transection of the hypogastric nerves did not affect remodeling of collagen or the census of macrophages or the density of nerve fibers in the cervix. These findings support the contention that enhanced innervation and immigration of immune cells are associated with remodeling of the cervix and parturition, but that a neural pathway other than the hypogastric nerve may participate in the process of cervical ripening.