Bladder inflammation and hypogastric neurectomy influence uterine motility in the rat (original) (raw)
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Effects of hypogastric neurectomy on escape responses to uterine distention in the rat
Pain, 1999
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 ~g/day of prostaglandin PF2c~ 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. @ 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.
AJP: Regulatory, Integrative and Comparative Physiology, 2006
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.
Fertility and Sterility, 2006
Objective: To determine, in rats, how surgically induced endometriosis and a control surgery (partial hysterectomy; sutures in abdomen) affects micturition thresholds and bladder vascular permeability. Design: Two animal studies, each performed in three groups of urethane-anesthetized rats in proestrus. Setting: Academic facility. Animal(s): Seventy-three female, regularly cycling Sprague-Dawley rats studied in proestrus. Intervention(s): Surgical induction of endometriosis (ENDO), surgical control (shamENDO), intact control (NoSURG), and bladder inflammation via intravesicular turpentine in all three groups. Main Outcome Measure(s): [1] Micturition thresholds (MTs; volume voiding thresholds), as measured by repetitive transurethral cystometry before and after bladder inflammation and [2] bladder inflammation, as assessed by extravasation of Evans Blue dye. Result(s): In the uninflamed bladder, MTs were significantly lower and dye extravasation significantly higher in ENDO rats than in shamENDO and NoSURG rats. Bladder inflammation increased dye extravasation in all groups and reduced MTs in the NoSURG and ENDO rats, but not in the shamENDO rats. Conclusion(s): Endometriosis reduces MTs and produces signs of inflammation in the healthy bladder. Surprisingly, the control surgical procedure (partial hysterectomy; sutures on mesenteric blood vessels) protects bladder reflexes from the influence of bladder inflammation, a condition that is named silent bladder inflammation. Such cross-system inducing and masking effects have important clinical relevance.
Neuroanatomic and behavioral correlates of urinary dysfunction induced by vaginal distension in rats
Neuroanatomic and behavioral correlates of urinary dysfunc-tion induced by vaginal distension in rats..—The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P 0.001) and the length of the motor branch of the sacral plexus (P 0.05), DNC (P 0.05), and vesical nerves (P 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P 0.05) and detrusor (P 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals. external urethral sphincter; dorsal nerve of the clitoris; major pelvic ganglion; micturition MICTURITION consists of two phases: storage and urine expulsion. During storage, the detrusor is relaxed while the bladder neck and urethra are activated, preventing involuntary bladder emptying (11). Extrinsic elements such as the levator ani muscle also contribute to the maintenance of continence (3). When the bladder reaches its threshold volume, spinal and supraspinal reflexes are triggered to induce bladder contraction and urethral relaxation, and urine flows through the urethra (11). Damage to the lower urinary tract and/or its innervation can induce urinary dysfunction (3, 29, 41). Urinary dysfunction affects the health of many women (60). Stress urinary incontinence has been described as involuntary loss of urine during effort and is the most prevalent urinary disorder related to vaginal childbirth, which is known to injure the pudendal nerve and denervate the external urethral sphinc-ter (EUS) (3, 15, 57). Maternal pelvic viscera and nerve damage results from the difficulty of human childbirth due the large fetal head and brain relative to the maternal pelvis size. Neonates at birth have heads that are close to the size of the maternal birth canal through which they must pass during the second stage of parturition (48). Births of fetuses over 4 kg or fetal malposition often prolong parturition (30), retaining the fetus in the pelvic cavity, the main anatomic resistance to fetal expulsion. Prolonged second stage of parturition is not uncommon in primi-gravid women, with an incidence of 37% (30, 55). Simulated delivery injury models, including vaginal disten-sion (VD) with a balloon in rats, have been created to better understand the injury process during parturition of women (20, 33). The diameter of the balloon and the duration of the distention can be adjusted to mimic the difficulty of parturition in women. A prolonged parturition can be modeled with VD of greater duration than the duration of parturition in intact rats (19, 34). Using the VD model, investigators have demonstrated bladder, urethral, and vaginal hypoxia (9), anatomic and functional damage to the EUS and its innervation (4, 21), and decreases in urethral resistance (26). Whether these VD-induced structural and functional changes are sufficient to cause signs of voiding dysfunction in awake animals is unknown. Most of the studies using simulated delivery injury models have focused on urethral neuromuscular injury (4, 21, 58). However, in addition to the pudendal nerve, there are other somatic and autonomic nerves running over or adjacent to the vaginal wall that could also be stretched during childbirth (40). Nonetheless, injury to pelvic, perineal, or bladder nerves has not been investigated in the rat VD model of simulated delivery. Moreover, no behavioral correlates of urinary dysfunction have been investigated after VD in conscious rats. The aim of the present study was to determine, in anesthe-tized rats, the VD-induced damage to genitourinary structures and nerves and, in conscious animals, the behavioral signs of urinary dysfunction. MATERIALS AND METHODS Experimental design. Thirty-four adult nulliparous Wistar female rats (250 –300 g body wt) were housed with water and food ad libitum and maintained on a 12:12-h light-dark cycle. The experimental protocol was approved by Tlaxcala University Committee on Labo
The Journal of Pain, 2008
The present studies examined the involvement of the rostral ventral medulla (RVM) in modulating the visceromotor response (VMR) evoked by urinary bladder distension (UBD) in adult female rats. The VMR was indexed by electromyographic (EMG) responses of the abdominal external oblique muscle to UBD. Experiment 1 showed that the predominant effect of electrical stimulation of the RVM in normal rats was to produce intensity-dependent inhibition of the VMR (54% of sites sampled). Facilitatory, biphasic, or no effects were obtained at the remaining sites. Experiment 2 showed that RVM-induced inhibition of the VMR was significantly attenuated by intraperitoneal (i.p.) administration of naloxone, but not saline vehicle. In Experiment 3, we examined the effect of lesions of the RVM in rats with inflamed bladders since previous research has shown that an endogenous opioid inhibitory system is engaged by bladder inflammation. Electrolytic lesions of the RVM, but not sham-lesions of the RVM, significantly increased the VMR to graded UBD in rats with augmented VMRs induced by prior inflammation of the bladder. The present data suggest that the RVM can inhibit the VMR to UBD acting in part via an opioid inhibitory system and that bladder inflammation can recruit the RVM to produce a net inhibitory effect on the VMR to UBD.
Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
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 g...
Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia
International urogynecology journal, 2016
Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Female Sprague-Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson's trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Bilateral pelvic nerve injury caused larger bladders with less SM content and increased colla...
Attenuation of pregnancy-induced analgesia by hypogastric neurectomy in rats
Brain Research, 1983
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.
International Urogynecology Journal, 2009
Introduction and hypothesis The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. Methods This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17βestradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers.
Neuromodulation in a rat model of the bladder micturition reflex
American Journal of Physiology-Renal Physiology, 2011
A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (Tmot) produced a delayed inhibition of the frequency of bladder con...