Hypogastric Neurectomy Research Articles

Inhibitory effects of aqueous extract of Hibiscus sabdariffa on contractility of the rat bladder and uterus

We examined an aqueous extract of Hibiscus sabdariffa calyces extracts (HSE) by close-arterial injection on micturition thresholds (MTs) and on uterine contractions (rate and amplitude). Five doses of HSE were examined (1, 5, 10, 50, and 100 mg/kg) in 3 groups of rats: controls, after bladder inflammation, and after bilateral hypogastric neurectomy. In some rats, uterine contractions were induced by injection of oxytocin (OT) and the effect of HSE was compared with that of nifedipine. HSE increased MTs in a dose-dependent manner in all groups. Neither atropine (0.1 mg/kg) nor propranolol (0.4 mg/kg) had significant effects on cystometric parameters. They also did not affect the responses obtained by HSE on cystometric parameters. As with bladder response, HSE inhibited both the rate and amplitude of uterine contractions in all groups in a dose-dependent manner. The uterine response to HSE was not affected by administration of either atropine or propranolol. A slight, but significant, reduction of contraction amplitude by HSE in the OT precontracted uteri was only noted at a dose of 500 mg/kg. Nifedipine was more potent than HSE in reducing uterine contraction amplitude. The present work documents inhibition by HSE of the rat bladder and uterine contractility in a dose-dependent manner via a mechanism unrelated to local or remote autonomic receptors or calcium channels. However, further investigation is needed to establish the exact mechanism of action.

Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve

Central nervous system neurons process information converging from the uterus, colon, and bladder, partly via the hypogastric nerve. This processing is influenced by the estrous cycle, suggesting the existence of an estrous-modifiable central nervous system substrate by which input from one pelvic organ can influence functioning of other pelvic organs. Here, we tested predictions from this hypothesis that acute inflammation of colon, uterine horn, or bladder would produce signs of inflammation in the other uninflamed organs (increase vascular permeability) and that cross-organ effects would vary with estrous and be eliminated by hypogastric neurectomy (HYPX). Under urethane anesthesia, the colon, uterine horn, or bladder of rats in proestrus or metestrus, with or without prior HYPX, was treated with mustard oil or saline. Two hours later, Evans Blue dye extravasation was measured to assess vascular permeability. Extravasation was increased in all inflamed organs, regardless of estrous stage. For rats in proestrus, but not metestrus, either colon or uterine horn inflammation significantly increased extravasation in the uninflamed bladder. Much smaller cross-organ effects were seen in colon and uterine horn. HYPX reduced extravasation in the inflamed colon and inflamed uterine horn, but not the inflamed bladder. HYPX eliminated the colon-to-bladder and uterine horn-to-bladder effects. These results demonstrate that inflaming one pelvic organ can produce estrous-modifiable signs of inflammation in other pelvic organs, particularly bladder, and suggest that the cross-organ effects involve the hypogastric nerve and are at least partly centrally mediated. Such effects could contribute to co-occurrence and cyclicity of distressing pelvic disorders in women.

Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve

Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies have suggested that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included sham ovariectomy (sham OVX), ovariectomy (OVX), OVX with estradiol replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed using repeated cystometrograms (CMGs) to measure micturition thresholds (MT) before and hourly for 3 h after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX group. As expected, bladder inflammation induced bladder hyperreflexia in sham OVX rats (studied in estrus). This hyperreflexia was eliminated by OVX and restored by either estradiol replacement or HYPX. Combining estradiol replacement and HYPX (i.e., OVX+E+HYPX) did not increase the severity of bladder hyperreflexia compared with either manipulation alone. These results indicate that the bladder hyperreflexia that is induced by bladder inflammation requires the presence of estradiol and suggest that this hormonal modulation is exerted via the sympathetic control of the bladder, possibly via an increase of beta-adrenergic inhibitory actions on the detrusor muscle. Similar mechanisms may contribute to bladder disorders in postmenopausal women.

Evaluation of a selective neurectomy model for low urethral pressure incontinence in female dogs

To develop a model of low urethral pressure incontinence and compare the relative contributions of the pudendal and hypogastric nerves with urethral function by performing selective neurectomy and ovariohysterectomy in dogs. 19 healthy Foxhounds. Dogs were allocated into 2 groups. The first group (10 dogs) underwent bilateral hypogastric neurectomy and ovariohysterectomy and subsequent bilateral pudendal neurectomy. The second group (9 dogs) underwent bilateral pudendal neurectomy and subsequent hypogastric neurectomy and ovariohysterectomy. Urethral pressure profilometry and leak point pressure (LPP) tests were performed before and after each neurectomy. Before surgery, mean +/- SD LPP and maximal urethral closure pressure (MUCP) in all dogs were 169.3 +/- 24.9 cm H2O and 108.3 +/- 19.3 cm H2O, respectively; these values decreased to 92.3 +/- 27 cm H2O and 60.7 +/- 20.0 cm H2O, respectively, after both selective neurectomy surgeries. There was a progressive decline of LPP after each neurectomy; however, MUCP decreased only after pudendal neurectomy. Fifteen dogs had mild clinical signs of urinary incontinence. All dogs appeared to have normal bladder function as indicated by posturing to void and consciously voiding a full stream of urine. Urinary tract infection did not develop in any dog. Hypogastric and pudendal neurectomy and ovariohysterectomy caused a maximum decrease in LPP whereas pudendal neurectomy caused a maximum decrease in MUCP. IMPACT ON HUMAN MEDICINE: This model may be useful for evaluation of treatments for improving urinary control in postmenopausal women.

Contrasting effects of WIN 55212-2 on motility of the rat bladder and uterus.

Both the uterus and bladder contain cannabinoid (CB) receptors whose functions are poorly understood. Here, in urethane-anesthetized female rats in metestrus, we simultaneously compared the effects of close-arterial injections of the cannabinoid receptor agonist WIN 55,212-2 (WIN2) on uterine contractions (amplitude and rate) and micturition thresholds (MT) assessed by cystometry. Five doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and 1.5 micromol/kg) in three groups: (1) controls; (2) after bladder inflammation with intravesicular turpentine; and (3) after bilateral hypogastric neurectomy (HYPX). In some rats, drugs were delivered via the tail vein. Regarding bladder, WIN2 dose-dependently reduced MTs in all groups. Both bladder inflammation and HYPX significantly increased this effect. Regarding uterus, WIN2 dose-dependently increased uterine contraction amplitude. Bladder inflammation or HYPX significantly decreased this effect. Coinjection of the CB1 antagonist SR141716A (SR) (1.5 micromol/kg) and WIN2 (0.5 micromol/kg) abolished or reduced the effects of WIN2 in both organs. SR alone had significant effects only after HYPX, reducing both MT and uterine contraction amplitude. The vehicle (0.4% DMSO) and inactive enantiomer S(-)-WIN 55,212-3 were both ineffective. Close-arterial injections of WIN2 (0.5 micromol/kg) produced significantly larger effects in both organs than tail vein injections. These results indicate that, whereas WIN2 reduces bladder motility, it mainly increases uterine motility, likely via CB1 receptors located in the two organs. The opposing effects of bladder inflammation and HYPX on the potency of WIN in the two organs suggest a neurally mediated viscero-visceral interaction in which bladder inflammation influences uterine CB1 sensitivity, possibly by inhibiting adrenergic input to the uterus.

Contrasting Effects of WIN 55212–2 on Motility of the Rat Bladder and Uterus

Both the uterus and bladder contain cannabinoid (CB) receptors whose functions are poorly understood. Here, in urethane-anesthetized female rats in metestrus, we simultaneously compared the effects of close-arterial injections of the cannabinoid receptor agonist WIN 55,212–2 (WIN2) on uterine contractions (amplitude and rate) and micturition thresholds (MT) assessed by cystometry. Five doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and 1.5 μmol/kg) in three groups: (1) controls; (2) after bladder inflammation with intravesicular turpentine; and (3) after bilateral hypogastric neurectomy (HYPX). In some rats, drugs were delivered via the tail vein. Regarding bladder, WIN2 dose-dependently reduced MTs in all groups. Both bladder inflammation and HYPX significantly increased this effect. Regarding uterus, WIN2 dose-dependently increased uterine contraction amplitude. Bladder inflammation or HYPX significantly decreased this effect. Coinjection of the CB1 antagonist SR141716A (SR) (1.5 μmol/kg) and WIN2 (0.5 μmol/kg) abolished or reduced the effects of WIN2 in both organs. SR alone had significant effects only after HYPX, reducing both MT and uterine contraction amplitude. The vehicle (0.4% DMSO) and inactive enantiomerS(−)-WIN 55,212–3 were both ineffective. Close-arterial injections of WIN2 (0.5 μmol/kg) produced significantly larger effects in both organs than tail vein injections. These results indicate that, whereas WIN2 reduces bladder motility, it mainly increases uterine motility, likely via CB1 receptors located in the two organs. The opposing effects of bladder inflammation and HYPX on the potency of WIN in the two organs suggest a neurally mediated viscero-visceral interaction in which bladder inflammation influences uterine CB1 sensitivity, possibly by inhibiting adrenergic input to the uterus.

Bladder inflammation and hypogastric neurectomy influence uterine motility in the rat

How pathophysiology of one pelvic organ influences the physiology of another is poorly understood. Here we compared the influence of bladder inflammation and hypogastric neurectomy (HYPX) on uterine contractions and bladder reflexes in urethane-anesthetized rats. Uterine contractions were measured via a latex balloon in one uterine horn. Bladder reflexes were assessed by micturition thresholds (MT) obtained cystometrographically. Whereas bladder inflammation significantly increased bladder reflexes (i.e., reduced MTs), it significantly decreased uterine contraction rate. Whereas HYPX produced small significant decreases in MT, it decreased the rate and significantly increased the amplitude of uterine contractions. These results indicate that bladder pathophysiology can influence uterine contractions and that some of this influence may be via the hypogastric nerve. Such viscero–visceral interactions likely involve spinal cord mechanisms and may have considerable clinical relevance.

Gestational and ovarian sex steroid antinociception: relevance of uterine afferent and spinal α2-noradrenergic activity

Pregnancy is associated with an antinociception that is multifactorial and results from spinal ( κ/ δ) opioid antinociceptive pathways as well as peripheral processes (ovarian sex steroids, uterine afferent neurotransmission). The present results provide the first indication that the full manifestation of pregnancy-induced analgesia also requires a supraspinal component. The analgesia of gestation or its hormonal simulation (via estrogen and progesterone administration; HSP) is substantially attenuated (≥60%) following blockade of spinal α 2 (but not α 1) adrenergic receptors. HSP antinociception is also attenuated by transection of the hypogastric nerve, the magnitude of which is indistinguishable from that produced by spinal α 2 receptor blockade. Additionally, hypogastric neurectomy abolishes the component of the antinociception associated with HSP that is mediated by spinal α 2 receptors. This suggests that the augmented spinal noradrenergic activity during HSP is not due to activation at the terminal of noradrenergic spinal projection neurons but requires supraspinal activity. It is suggested that enhanced spinal noradrenergic activity amplifies ongoing spinal κ/ δ antinociception as has been observed following the concomitant intrathecal application of α 2 and opioid agonists. The current observations underscore the importance of visceral afferent activity as well as its modulation by a female-specific hormonal milieu to the efficacy of endogenous spinal opioid antinociception.

Effects of hypogastric neurectomy on escape responses to uterine distention in the rat

Anatomical data indicate that the rat uterine horn is innervated primarily by afferent fibers in the hypogastric nerves, suggesting that hypogastric neurectomy, but not pelvic or pudendal neurectomy, should eliminate behavioral responses to uterine horn stimulation. To test this hypothesis, detection and escape responses of rats to different volumes of uterine horn distention (via an indwelling intrauterine balloon) were compared before and after bilateral hypogastric ( n = 9), sham-hypogastric ( n = 3), pelvic ( n = 3), or pudendal ( n = 2) neurectomies. As predicted, sham-hypogastric, pelvic, and pudendal neurectomies had no effect on the rats' responses. However, although hypogastric neurectomy completely eliminated responses in five rats whose postmortem evaluation revealed no signs that the uterine balloons had evoked any pelvic pathophysiology, the neurectomy had no effect on the responses of an additional four rats. Postmortem evaluation of these rats revealed gross signs of severe pathology in the vicinity of the balloon in two rats, and evidence that the balloon had shifted caudally so that it was stimulating the cervix rather than the uterine horn in a third. In the fourth rat, pathophysiology had been deliberately induced by the prior implantation of a small pellet that released ∼1 μg/day of prostaglandin PF2α over the uterine horn. Similar findings have been reported in clinical studies on the efficacy of hypogastric (‘presacral’) neurectomy for dysmenorrhea. Together, the findings support the hypothesis that the major source of afferent innervation of the uterine horn in healthy rats and women is the hypogastric nerve but that the situation changes under conditions of pelvic pathology. Such changes could include additional activation of afferent fibers in nerves that supply other pelvic organs, activation by the uterine pathophysiology of latent uterine innervation from afferent fibers in the pelvic, vagus or ovarian plexus nerves, or some form of central sensitization.

Neural mechanisms accounting for the increase in blood pressure and heart rate during vagino-cervical stimulation

The rise in blood pressure and heart rate produced by the mechanical stimulation of the uterine cervix (VS) was examined after adrenalectomy, after pelvic or hypogastric neurectomies or after spinal cord transection in anesthetized rats. Neither adrenalectomy, nor hypogastric neurectomy prevented the rise in heart rate and blood pressure produced by VS. After the spinal cord transection at T6 level, VS was still able to produce the rise in blood pressure. However, the rise in blood pressure was significantly lower than that produced in the same animals before the transection. No changes in heart rate were produced by VS after spinal cord transection. This result can be explained because this level of transection prevents the reach of the afferent inflow to the superior cervical ganglia. Pelvic neurectomy abolished completely the effects of VS on blood pressure and heart rate. Low intensity (1–2 times the threshold) electrical stimulation of the pelvic nerve produced a rise in blood pressure. Even though heart rate increased during electrical stimulation, the change in heart rate was not statistically different from the pre-stimulation value. These results suggest that the changes in blood pressure and heart rate produced by VS represent a neuronal reflex response mediated by the pelvic nerve. The fact that the effects of VS on blood pressure persist in spinal cord-transected animals suggests that the reflex is integrated at the spinal level. However, the cardiovascular responses to VS were significantly lower than before transection, suggesting that supraspinal centers are also involved in the reflex.

Pelvic neurectomy blocks oxytocin-facilitated sexual receptivity in rats

The effect of bilateral pelvic, hypogastric, or pudendal neurectomy on oxytocin-induced facilitation of lordosis behavior was examined in ovariectomized, estrogen, and progesterone primed female rats. Oxytocin-induced facilitation of lordosis behavior was significantly decreased following bilateral pelvic, or combined bilateral pelvic and hypogastric neurectomy. Hypogastric only or pudendal only neurectomy had no effect on the facilitation of lordosis behavior after systemic administration of oxytocin. These results suggest that the integrity of the pelvic nerve is necessary and sufficient to mediate the stimulatory effects of systemically administered oxytocin on receptivity.

Analgesia is produced by uterocervical mechanostimulation in rats: roles of afferent nerves and implications for analgesia of pregnancy and parturition

Afferent activity from the reproductive tract activates intrinsic pain attenuating processes. For example, analgesia results from vaginocervical mechano-stimulation in nonpregnant rats and occurs during pregnancy and parturition. In the present study, the effect of uterocervical mechanostimulation on pain thresholds was investigated in order to determine whether direct stimulation of the uterine cervix could play a role in the analgesia of pregnancy. Uterocervical mechanostimulation was applied to nonpregnant rats via a silastic disc implanted in the uterus. The disc abutted against the cervix and was attached to a thread externalized through the vaginal orifice. Application of a force of 150 g, but not 100 g, produced a significant increase in tail flick latency (110.4 ± 40.6%, P < 0.03). This effect was abolished by pelvic neurectomy, but was not altered by hypogastric neurectomy. Stimulation of the uterine cervix in combined pelvic and hypogastric neurectomy rats produced a decrease in tail flick latency. These results indicate that the analgesia that occurs during pregnancy and/or parturition may result, at least in part, from the uterocervical mechanostimulation that occurs during this condition.

Differential roles of hypogastric and pelvic nerves in the analgesic and motoric effects of vaginocervical stimulation in rats

Bilateral transection of the pelvic and/or hypogastric nerves, which convey afferent activity from the reproductive tract, was performed to ascertain the role of these nerves in the analgesic and motoric effects of vaginocervical mechanostimulation (VS) in rats. Two indices of analgesia were used: tail flick latency to radiant heat (TFL) and vocalization threshold to electrical shock of the tail (Voc-T). Nerve cuts were performed at least one week prior to behavioral testing. Bilateral transection of both the pelvic and hypogastric nerves eliminated the analgesic effects of VS on the TFL and Voc-T tests. Bilateral transection of only the pelvic nerves reduced the number of rats showing maximal VS-induced elevation in TFL, without altering the effect of VS on Voc-T. By contrast, bilateral transection of only the hypogastric nerves attenuated the Voc-T-elevating effect of VS, without reducing the effect of VS on elevating TFL. The effects of VS on producing immobility, hindlimb extension and blockage of hindlimb withdrawal to foot pinch were eliminated by combined bilateral pelvic and hypogastric neurectomy. However, bilateral transection of either nerve alone did not significantly alter the efficacy of VS in producing these effects. These findings indicate that the pelvic and hypogastric nerves contribute to the immobility- and extensor-inducing, and flexor-inhibiting effects of VS, and differentially mediate the analgesia-producing effects of VS.

Sympathetic innervation of the reproductive organs of the male opossum, Didelphis albiventris (Lund, 1841).

The dissection of nerves and ganglia anatomically related to the pelvic organs revealed one inferior mesenteric ganglion, two testicular ganglia, two hypogastric nerves, two pelvic ganglia and two pelvic nerves. The histochemical demonstration of catecholamines by a glyoxylic acid fluorescence method revealed a rich sympathetic innervation in the ductus deferens, in the three segments of the prostate and in the convoluted ductuli efferentes. The testis, epididymis and all three pairs of bulbourethral glands presented fluorescent nerve fibers only around blood vessels. Removal of the inferior mesenteric and testicular ganglia, and hypogastric neurectomy with our without ligature and sectioning of testicular arteries, had no effect on the density of the nonvascular fluorescent fibers. Removal of the periprostatic tissue caused complete denervation of the prostate and marked denervation of the ductuli efferentes and ductus deferens. Small ganglia containing fluorescent nerve cell bodies were found close to the capsule of the prostate. The results indicate that short adrenergic neurons are responsible for the sympathetic innervation of the reproductive organs of the male opossum.

Intrinsic neuromuscular defects in the neurogenic bladder: IX. Effects of combined parasympathetic decentralization and hypogastric neurectomy on neuromuscular ultrastructure of the feline bladder base

AbstractPrevious studies have shown that unilateral decentralization of the feline bladder by sacral ventral rhizotomy results in ultrastructural neuromuscular changes in the bladder base. In the present study, the neuromuscular ultrastructure of the feline bladder base was studied in twenty sexually mature adult male cats 1–4 and 6–10 weeks following bilateral sacral rhizotomy, alone and combined with hypogastric neurectomy. The former procedure resulted in initial degeneration of cholinergic axons with loss of their neuroeffector junctions, but the adrenergic axons and neuroeffector junctions were preserved; within 6–10 weeks, the bladder base became re‐innervated by regenerated cholinergic, increased adrenergic, and abundant probable copeptidergic axons. In contrast, combined sacral rhizotomy and hypogastric neurectomy resulted in persistent (up to 10 weeks) degeneration of both cholinergic and adrenergic axons with loss of their neuroeffector junctions, and no adrenergic hyperinnervation, with only a modest increase in probable copeptidergic axons in long‐term samples. Our observations indicate that intact efferent sympathetic pathways are essential for eventual cholinergic re‐innervation and adrenergic hyperinnervation of the decentralized bladder and suggest that the latter is an important factor in the development of vesical hypertonicity in lower‐motor neuron lesions. On this basis, we introduce the concept that two functional types of the lower motor neurogenic bladder–i.e., the hypertonic with intact and the normotonic with injured efferent sympathetic pathways–may be distinguishable morphologically by ultrastructural study of the vesical muscularis.

575 - Effects of Combined Sacral Decentralization and Hypogastric Neurectomy on Intrinsic Innervation of the Feline Bladder Base

575 - Effects of Combined Sacral Decentralization and Hypogastric Neurectomy on Intrinsic Innervation of the Feline Bladder Base

Attenuation of pregnancy-induced analgesia by hypogastric neurectomy in rats

This study confirms previous observations of an increase in pain threshold prepartum followed by a decrease postpartum. Moreover hypogastric nerve transection significantly attenuated the analgesia of pregnancy by a factor of 5 but did not abolish it. Thus, the hypogastric nerve plays a major, but not exclusive, role in the analgesia of pregnancy.

Experimental evidence indicating that the penis of the rat is innervated by short adrenergic neurons.

AbstractTo determine if the penis of the rat is supplied by long or short adrenergic neurons, hypogastric and perivascular neurectomies were performed. Reserpine, a drug which depletes the store of norepinephrine from long adrenergic nerves more rapidly than from short adrenergic neurons, has also been used to aid in characterizing this innervation. Hypogastric neurectomy, with or without denervation of the common iliac vessels, had no effect on the density or fluorescence intensity of adrenergic fibers in the rat penis. The long adrenergic fibers to the atria did not fluoresce in reserpine‐treated rats; however, fluorescent adrenergic fibers in the penis and vas deferens remained visible. Reserpine depressed atrial levels of norepinephrine by 75%, while norepinephrine in the penis and vas deferens was reduced only by 32% and 29%, respectively. The absence of any effect of hypogastric neurectomy on the adrenergic fibers of the penis indicates that such fibers arise from neurons distal to the site of lesion of the hypogastric nerves. This result and the similar response of the vas deferens and penis to reserpine strongly suggest that the penis of the rat is supplied by short adrenergic neurons.