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Preganglionic fibers in the rat hypogastric nerve project bilaterally to pelvic ganglia.

Stimulation of the hypogastric nerve (HGN) often evokes bilateral responses in some pelvic organs. Retrograde labeling studies indicate that axons of postganglionic neurons often cross to the opposite side. However, there is little information available as to whether preganglionic fibers in the HGN have a contralateral projection to pelvic ganglia. A retrograde tracer was injected into the left major pelvic ganglion (MPG) in rats receiving various lesions of preganglionic nerves (HGN and pelvic nerve, PN). The lumbar spinal cord was then examined for location and number of dye-filled neurons. In a second approach, the incidence of synaptophysin immunoreactivity (SN-IR) perineuronal profiles (baskets) was examined in the MPG and in the accessory pelvic ganglia (APG) after nerve lesions. Labeled neuronal profiles were found in spinal cord nuclei (Lumbar1-2) after dye injection of the MPG in animals with an intact contralateral HGN. Cutting both HGNs virtually eliminated dye labeling in the lumbar cord, as did severing commissural branches (CB) between pelvic ganglia (leaving the contralateral HGN intact). Some SN-IR baskets were found in the left APG when only the contralateral HGN was intact, but baskets were rare when all four preganglionic nerves were cut. It could not be determined whether the HGN projects to the contralateral MPG, since SN-IR baskets were numerous in the MPG even when all four nerves were cut. This study has shown that some preganglionic fibers in the HGN synapse on neurons in contralateral pelvic ganglia. Both the APG and MPG receive contralateral innervation, but it is likely that neurons in the APG are the primary target of this input. Thus, in addition to crossing postganglionic fibers, a portion of the bilateral control of pelvic tissues is accomplished by preganglionic fibers which target autonomic neurons in contralateral ganglia.

Animals↗

Pelvic cancer pain.

Pelvic cancer causes several types of pain, i.e., visceral, neuropathic, and somatic pain. Somatic pain is due to stimulation of nociceptors in the integument and supporting structures, namely, striated muscles, joints, periosteum, bones, and nerve trunks by direct extension through fascial planes and their lymphatic supply. In 60% of patients with malignant disease of soft tissues, nerve trunk, and sacral invasion from carcinoma of the cervix, uterus, vagina, colon, rectum, and other tissues in women, and from penile, prostate, and colorectal carcinoma and sarcoma in men, they have neuropathic pain. The infiltration of the perineal nerves results in lumbosacral plexopathies and complete destruction of the nerve, including perineural lymphatic invasions producing symptomatic sensory loss, causalgia, and deafferentation. Visceral pain is the result of spasms of smooth muscles of hallow viscus; distortion of capsule of solid organs; inflammation; chemical irritation; traction or twisting of mesentery; and ischemia, or necrosis, and encroachment of pelvis and presacral tumors. Pain of these types is managed by different modalities depending on the age of the patient, the expected life expectancy, availability of invasive and non-invasive pain control modalities, and the resources of the patient, community, and health care agencies. Patients with pelvic cancer can live with less pain due to better pain-control modalities that are available today with the help of dedicated and caring algologists.

Afferent Pathways↗

Neuroendocrine cells and nerves in the prostate of the guinea pig: effects of peripheral denervation and castration.

BACKGROUND: Neuroendocrine (NE) cells and nerves in the prostate gland are thought to play a central role in the regulation of growth, cellular differentiation and homeostasis of secretory activity. The objective of this experimental study was to describe the effects of peripheral denervation and castration on NE cells and nerves in the guinea pig prostate. METHODS: Guinea pigs underwent sham-operation, unilateral and bilateral hypogastric nerve resection, extirpation of the right anterior major pelvic ganglion (AMPG), autotransplantation of prostatic tissue and castration. Cryostat sections of prostatic tissue were examined with immunohistochemistry by using serotonin (5-HT) and chromogranin A (CgA) and various neuropeptides. RESULTS: The number of 5-HT-IR NE cells was four-fold higher than CgA-IR NE cells. The innervation pattern was uniform throughout the gland with subepithelial nerves in close proximity to NE cells. Autotransplants of prostatic tissue showed total loss of nerves, but the number and morphology of 5-HT-IR NE cells were unaltered. Extirpation of the right AMPG showed significant reduction in prostate weight, decreased density of nerve terminals in the superior part of the ipsilateral prostate, whereas the number and morphological feature of 5-HT-IR NE cells remained unaffected in the entire prostate. Castration induced atrophy of the gland with a significant reduction in weight (unpaired t-test, P < 0.001), but without effect upon 5-HT-IR NE cells. CONCLUSIONS: The guinea pig seems to be a useful animal model for studies on the role of the NE cells in the prostate. NE cells seem to be independent of innervation and androgens. It seems that other factors influence the NE cell population to a greater extent.

Animals↗

Reconstruction of the canine pelvic nerve and its application to bladder transplantation.

The pelvic nerve (PN) plays a crucial role in control of bladder function. However, repair of the PN during operation or transplantation of the urinary bladder preserving PN control has never been reported. This study was undertaken to explore the possibilities of restoring PN function to the canine bladder after PN-PN reattachment and of transplanting the bladder while preserving PN function. Responses of the bladder to electrical stimulation of the PN were examined in dogs that had undergone PN-PN reattachment or auto-transplantation of the bladder with PN-PN reattachment. Cystometry was performed in dogs that had undergone bladder transplantation. Eighteen months after unilateral PN-PN reattachment, stimulation of each of five PNs sutured in five dogs elicited elevation of bladder pressure. Twelve months after bilateral PN-PN reattachments in five dogs, eight of 10 PNs stimulated elicited elevation of bladder pressure. Three of five dogs that had undergone auto-transplantation of the bladder showed a long survival. Nine months after the operation, each of the six PNs stimulated in the three dogs elicited elevation of bladder pressure. Voiding reflex was observed in two of the three dogs on cystometry. All the 13 dogs examined above preserved sufficient bladder capacity and all but one demonstrated small volume of residual urine. The above results indicate that the function of the PN to the canine bladder can be restored after PN-PN reattachment and that transplantation of the bladder preserving control of the PN is possible.

Animals↗

Neural control of internal anal sphincter function.

The effect on anal tone of electrical stimulation of the presacral (hypogastric) sympathetic nerves has been studied in eight patients during abdominal rectopexy or restorative proctocolectomy. A sharp fall in anal pressure occurred in seven patients (mean fall 59 cmH2O; range 35-80 cmH2O). In one patient given a beta- and alpha-sympathetic blocking drug (labetalol 200 mg) intra-operatively, the anal pressure decreased by 15 cmH2O. These observations show that stimulation of the presacral sympathetic nerves causes relaxation of the internal anal sphincter and implies that these nerves may induce relaxation of the sphincter in vivo. The pathway of the recto-anal reflex has been studied intra-operatively in three patients undergoing rectal excision. The recto-anal reflex is present after presacral nerve blockade and after full mobilization of the rectum, but is abolished by circumferential rectal myotomy. The reflex has a local intramural pathway. This observation validates the assumption that absence of this reflex is a feature of aganglionosis, as in Hirschsprung's disease.

Adrenergic Fibers↗

A preganglionic autonomic nucleus in the dorsal gray commissure of the lumbar spinal cord of the rat.

The distribution in the spinal cord of the rat of preganglionic neurons sending fibers into the hypogastric nerve was determined with the retrograde transport of horseradish peroxidase (HRP). Labeled cells were present in the intermediate gray matter of spinal segments L1-L2. The majority (81%) of HRP-filled cells formed a continuous column along the midline in the dorsal gray commissure. This cell column was termed the dorsal commissural nucleus (DCN). The remainder of HRP-labeled cells were present bilaterally in the middle and lateral regions of the intermediate gray; the majority of the latter cells were located along the lateral border of the intermediate gray. The present finding of a midline preganglionic autonomic cell column in the spinal cord of a mammal is contrary to previous reports, in which sympathetic preganglionic neurons have been localized primarily in the lateral intermediate gray. The DCN may be species-specific and related to the system of short adrenergic neurons present in the pelvis.

Animals↗

An analysis of the axon populations in the nerves to the pelvic viscera in the rat.

The present study uses selective surgical ablations combined with electron microscopic analyses to determine the number of axons in various categories in rat hypogastric, pelvic, and pudendal nerves, these being the nerves to the pelvic viscera in this animal. Unmyelinated fibers predominate in all of these nerves. One of the most significant findings is that the pelvic nerve contains almost as many postganglionic sympathetic fibers as the hypogastric nerve. Previous investigators thought that the pelvic nerve supplied the parasympathetic inflow and the hypogastric nerve the sympathetic inflow to the pelvic viscera. The finding that there is a sizable sympathetic component in the pelvic nerve negates this idea, at least for the rat, and presumably calls for a reevaluation of the syndromes that arise from pelvic as opposed to hypogastric nerve section. Other findings of interest are (1) that there are unmyelinated efferent axons in the pudendal nerve, indicating that the pudendal is not a typical somatic nerve, (2) that the hypogastric nerve has a very small sensory component, and (3) that there are fibers surviving in the distal stumps of all these nerves, particularly the pelvic and hypogastric nerves.

Adrenergic Fibers↗

The afferent and sympathetic components of the lumbar spinal outflow to the colon and pelvic organs in the cat. I. The hypogastric nerve.

The cell bodies of the lumbar sensory and sympathetic pre- and postganglionic neurons that project to the pelvic organs in the hypogastric nerve of the cat have been labeled retrogradely with horseradish peroxidase applied to the central end of their cut axons. The numbers, segmental distribution, location, and size of these labeled somata have been determined quantitatively. Afferent and preganglionic cell bodies were located bilaterally in dorsal root ganglia and spinal cord segments L3-L5, with the maximum numbers in L4. Very few cells lay rostral to L3. Afferent cell bodies were generally very small in cross-sectional area relative to the entire population in the dorsal root ganglia. Most of the preganglionic cell bodies lay clustered just medial to the region of the intermediolateral column and extended caudally well beyond its usual limit in the upper part of L4. These neurons were, on the average, larger than the cells of the intermediolateral column itself, with the largest cells lying in the most medial positions. Most of the post-ganglionic somata were in the ipsilateral distal lobe of the inferior mesenteric ganglion, while some (usually less than 10%) lay in accessory ganglia along the lumbar splanchnic nerves and in paravertebral ganglia L3-L5. Postganglionic somata in the inferior mesenteric ganglion were larger than both labeled and unlabeled ganglion cells in the paravertebral ganglia. From the data, it is estimated that about 1,300 afferent neurons, about 1,700 preganglionic neurons, and about 17,000 postganglionic neurons project in each hypogastric nerve in the cat.

Animals↗

The afferent and sympathetic components of the lumbar spinal outflow to the colon and pelvic organs in the cat. III. The colonic nerves, incorporating an analysis of all components of the lumbar prevertebral outflow.

The cell bodies of the lumbar sensory and sympathetic pre- and postganglionic neurons that project to the colon along the inferior mesenteric artery of the cat have been labeled retrogradely with horseradish peroxidase applied to the central end of their cut axons. The numbers, segmental distribution, location, and size of these labeled somata have been determined quantitatively. Afferent cell bodies were symmetrically distributed bilaterally in dorsal root ganglia T13-L5, with the maximum number (about 80%) in L3 and L4 and most of the rest in L2. Labeled afferent somata were small relative to the entire population of DRG cells. Occasionally a few preganglionic somata were labeled in the intermediate zone of L3 and L4 spinal cord segments. Postganglionic cell bodies were labeled bilaterally in the proximal lobes of the inferior mesenteric ganglion (70-95%), in accessory ganglia of the intermesenteric nerve and of the lumbar splanchnic nerves, and in lumbar paravertebral ganglia. The segmental distribution in the lumbar sympathetic trunk was symmetrical on both sides and was the same as that of the afferent cells. Labeled postganglionic cell bodies in both the IMG and the accessory ganglia were larger than labeled and unlabeled ganglion cells in the paravertebral ganglia. From these data, it is estimated that about 2,100 afferent neurons and about 29,000 postganglionic neurons project in the lumbar colonic nerves. In conjunction with equivalent data for the hypogastric and lumbar splanchnic nerves, the results provide a quantitative and spatial description of the afferent and efferent components of the lumbar innervation of the colon and pelvic viscera.

Animals↗

The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat.

The spinal distribution of sympathetic preganglionic neurons (PGN) and visceral primary afferent neurons sending axons into the hypogastric nerve of the cat has been studied with HRP tracing techniques. After application of HRP to the cat hypogastric nerve, labeled PGN were identified in segments L2-L5. Most of these neurons were oriented transversely and were divided approximately equally between two nuclei: the principal nucleus and the intercalated nucleus. Cells were distributed in clusters at 160-361-microns intervals along the length of the cord. Sensory neurons were labeled in dorsal root ganglia from T12 to L5. Central axons of these visceral afferents were observed in the medial half of Lissauer's tract from T13 to L7. Afferent axon collaterals extended through lamina I on both sides of the dorsal horn but were most prominent on the lateral side, where they continued into lateral lamina V and VII, often overlapping the dorsal dendrites of PGN in this region. Labeled afferent projections exhibited a periodic distribution in lamina I with clusters of axons occurring at 235-343-microns intervals in the rostrocaudal axis. The central projection of hypogastric nerve primary afferents was qualitatively similar to the distribution of visceral afferent projections at other levels of the spinal cord.

Animals↗

Sexual dimorphism in sympathetic preganglionic neurons of the rat hypogastric nerve.

Horseradish peroxidase (HRP) applied to one hypogastric nerve labelled sensory neurons in T11-L3 dorsal root ganglia (DRG) bilaterally and preganglionic neurons (PGN) in the spinal cord segments T13-L3. An average of 130 small DRG neurons were labelled per animal (male or female). These were concentrated in the L1 + L2 DRGs (92%). About 75% were located ipsilateral to the site of HRP application. Central projections from DRG neurons were noted throughout Lissauer's tract and in the marginal zones (medial and lateral) near the borders of Lissauer's tract. A short projection was also seen extending to the dorsolateral funiculus. More than 90% of the preganglionic neurons were located in segments L1 + L2. Most of these were found in the dorsal commissural nucleus (75%) and most of the remainder were located bilaterally in the intermediolateral columns. Somewhat more intermediolateral neurons were labelled on the ipsilateral side than on the contralateral side. There were a few intercalating neurons and a very few funicular cells. An average of 415 PGNs were labelled in the male animals and 110 in the females, demonstrating a strong sexual dimorphism. No dimorphism was found in the sensory components.

Animals↗

Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum.

The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.

Animals↗

Urinary retention and sympathetic sphincter obstruction in axonal Guillain-Barré syndrome.

A 62-year-old woman with axonal Guillain-Barré syndrome developed weakness and urinary retention simultaneously. The retention failed to recover for 10 months even after she regained the ability to walk. The patient exhibited no postural hypotension. Videourodynamics showed that the retention was caused not by the bladder paralysis but rather by internal (sympathetic) sphincter obstruction, which is extremely uncommon in peripheral neuropathies. We started the patient on an alpha-adrenergic antagonist, urapidil, at 30 mg/day, and this led to successful relaxation of the urethra and reduced the postvoid residual from 200 ml to less than 30 ml. The underlying mechanisms of urinary retention in our patient appeared to involve hyperactive lumbosacral sympathetic nerves. Urinary retention and sympathetic sphincter obstruction can thus be features of axonal Guillain-Barré syndrome.

Adrenergic alpha-Antagonists↗

Effects of the atypical neuroleptic clozapine on micturition parameters in anesthetized rats.

Clozapine, an atypical antipsychotic, has resulted in a number of reports of urinary disturbances in the clinical literature. We examined the effects of clozapine on urodynamic parameters in the anesthetized rat and compared the effects to those of the typical antipsychotic haloperidol and the selective D2 and D4 antagonists, raclopride and L-745,870, respectively. Clozapine abolished high-frequency oscillations (HFO) during the expulsion phase, and profoundly altered a number of other parameters (e.g., intercontraction interval and resting pressure). Clozapine did not affect the peak contraction pressure during cystometrograms but displayed peripheral inhibition of bladder contractions elicited by electrical stimulation of the pelvic nerve (possibly mediated via clozapine's anti-muscarinic effects). Haloperidol had less potent effects than clozapine since it reduced the amplitude of HFO to 25% of control and also affected several other parameters but without peripheral bladder inhibition. Raclopride only resulted in a modest decrease (approximately 70% of control) in the HFO and no alteration in other parameters. L-745,870 was effective only at highest dose tested suggesting that it might not be acting selectively at D4 receptors. Therefore, we propose that clozapine primarily interferes with the function of the external urethral sphincter. These effects can only be partly explained through antagonism of D2 receptors. Since both clozapine and haloperidol have interactions with other transmitter systems beside dopamine, we suggest that central antagonism of D2 receptors, coupled to central antagonism of another receptor system and peripheral muscarinic receptor blockade, may account for clozapine's potent effects on micturition.

Anesthesia↗