Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia (original) (raw)

Short-term functional and neuroregenerative response of the urethra to ovariectomy and vaginal distension in female rats

International Urogynecology Journal, 2005

The objective of this study was to investigate the effects of ovariectomy (OVX) and vaginal distension (VD) on leak point pressure (LPP) and pudendal nerve regenerative response in the female rat. Twenty rats underwent OVX 3 days prior to either VD or sham distension. Seventeen rats did not receive OVX but underwent either VD or sham distension. Four days after distension, LPP testing was performed. In situ hybridization for b II tubulin mRNA, an indicator of the neuroregenerative response, was performed on motoneurons of the pudendal nerve. In the non-OVX group, LPP was significantly decreased after VD. After OVX, the difference in LPP between VD and sham rats did not quite reach the level of statistical significance. There was a statistically significant interaction between the effects of OVX and VD on LPP. There was no significant difference in in situ hybridization results between any of the groups. No neuroregenerative response of motoneurons of the pudendal nerve was observed after either VD or OVX.

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

AJP: Regulatory, Integrative and Comparative Physiology, 2008

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence that is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats.

Effect of Estrogen on Urethral Function and Nerve Regeneration Following Pudendal Nerve Crush in the Female Rat

The Journal of Urology, 2006

We tested the hypothesis that estrogen promotes improvement in urethral function and nerve regeneration following bilateral pudendal nerve crush in ovariectomized female rats. Materials and Methods: A total of 52 female rats underwent ovariectomy 6 days before bilateral pudendal nerve crush. Estrogen and sham capsules were subcutaneously implanted at the time of nerve crush in 16 and 14 of these rats, respectively, while 22 served as unoperated controls. Seven days following nerve crush urethral LPP testing was performed using urethane anesthesia. Spinal cord sections containing motoneurons of Onufrowicz's nucleus were subjected to in situ hybridization to detect the expression of ␤ II tubulin mRNA, a marker of the neuroregenerative response. Results: Mean LPP Ϯ SEM was significantly decreased after pudendal nerve crush in sham treated animals compared to unoperated controls (32.1 Ϯ 6.8 vs 54.4 Ϯ 11.6 cm H 2 O). Rats with an estrogen implant had an LPP of 42.5 Ϯ 16.8 cm H 2 O, which was significantly greater than rats given sham implants and significantly less than unoperated controls. Rats that received an estrogen implant had increased ␤ II tubulin mRNA expression compared to those that received a sham implant.

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study

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.

Perioperative Betamethasone Treatment Reduces Signs of Bladder Dysfunction in a Rat Model for Neurapraxia in Female Urogenital Surgery

European Urology, 2012

Background-Information on autonomic neurapraxia in female urogenital surgery is scarce, and a model to study it is not available. Objective-To develop a model to study the impact of autonomic neurapraxia on bladder function in female rats, as well as to assess the effects of corticosteroid therapy on the recovery of bladder function in this model. Design, setting, and participants-Female Sprague-Dawley rats were subjected to bilateral pelvic nerve crush (PNC) and perioperatively treated with betamethasone or vehicle. Bladder function and morphology of bladder tissue were evaluated and compared with sham-operated rats.

Bladder inflammation and hypogastric neurectomy influence uterine motility in the rat

Neuroscience Letters, 2001

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. q

Functional studies on the cholinergic and sympathetic innervation of the rat proximal urethra: effect of pelvic ganglionectomy or experimental diabetes

Journal of Autonomic Pharmacology, 1989

Isolated rings of rat proximal urethra contracted in response to acetylcholine, noradrenaline, phenylephrine, tachykinins or field stimulation. In the presence of field stimulation-induced contractions, isoprenaline or CGRP produced an inhibitory effect on evoked contractions. 2 Electrical field stimulation produced frequency-related contractions which, when using trains of stimuli, consisted of a phasic and a tonic response. These contractions were abolished by tetrodotoxin (1 p~) but unaffected by hexamethoniurn (10 p~). 3 Atropine (3 ,UM) produced a partial inhibition of these nerve-mediated contractions, slightly more evident on the tonic than the phasic response. In the presence of atropine (3 p~) , phentolamine (3 ,UM) or prazosin (1-10 nM) produced an almost complete inhibition of the response to field stimulation. 4 After bilateral removal of the pelvic ganglia, electrical field stimulation was still able to induce tetrodotoxin-sensitive contractions of the rat proximal urethra. However, the inhibitory effect of atropine was much reduced as compared to controls, while the phentolamine-sensitive portion of the response was increased. 5 DMPP (0.1 mM) a nicotinic receptor agonist, produced a contraction (phasic and tonic components) which was strongly inhibited by hexamethonium (1 0 p~) , abolished by prazosin (1 ,UM) and reduced by tetrodotoxin (3 p~). 6 In urethral rings from diabetic rats (i.v. streptozotocin 7-9 weeks before) the contractile response to acetylcholine or noradrenaline as well as the response to field stimulation were unchanged as compared to controls. 7 Capsaicin (1 p~) produced an inhibitory effect on the nerve-mediated contractions of the rat proximal urethra. This response was abolished by pelvic ganglionectomy but was unaffected in streptozotocin-treated rats. 8 These findings provide functional evidence that both cholinergic and noradrenergic nerves mediate the contractions of the rat proximal urethra. In addition, capsaicin-sensitive sensory nerves can produce certain local motor responses through release of endogenous neuropeptides. In vivo studies are needed to examine the interplay between these differents sets of motor nerves in the regulation of proximal urethra motility.

Pudendal Nerve Stretch Reduces External Urethral Sphincter Activity in Rats

The Journal of Urology, 2012

Purpose: Most animal models of stress urinary incontinence simulate maternal injuries of childbirth since delivery is a major risk factor but they do not reproduce the nerve stretch known to occur during human childbirth. We hypothesized that pudendal nerve stretch produces reversible dysfunction of the external urethral sphincter. Materials and Methods: Female virgin Sprague-Dawley® rats were anesthetized with urethane. Bilateral pudendal nerve stretch or sham injury was performed for 5 minutes. External urethral sphincter electromyography and leak point pressure were recorded immediately before and after, and 10, 30, 60 and 120 minutes after pudendal nerve stretch. Post-pudendal nerve stretch results were compared to prestretch values and to values in sham injured animals. The pudendal nerves underwent qualitative histological assessment. The nucleus of Onuf was evaluated by immunohistochemistry and polymerase chain reaction for ␤-APP and c-Fos expression as markers of neuronal activity and injury. Results: A total of 14 rats underwent bilateral pudendal nerve stretch (9) or sham injury (5). Each nerve was stretched a mean Ϯ SEM of 74% Ϯ 18% on the left side and 63% Ϯ 13% on the right side. Electromyography amplitude decreased significantly immediately after stretch compared to before stretch and after sham injury (p ϭ 0.003) but it recovered by 30 minutes after stretch. There was no significant change in leak point pressure at any time. Two hours after injury histology showed occasional neuronal degeneration. ␤-APP and c-Fos expression was similar in the 2 groups. Conclusions: Acute pudendal nerve stretch produces reversible electrophysiological dysfunction but without leak point pressure impairment. Pudendal nerve stretch shows promise in modeling injury. It should be tested as part of a multi-injury, chronic, physiological model of human childbirth injury.

Estrogen Modulates the Spinal N -Methyl- d -Aspartic Acid-Mediated Pelvic Nerve-to-Urethra Reflex Plasticity in Rats

Endocrinology, 2006

The effects of gonadal steroids on glutamate-mediated pelvic nerve-to-urethra reflex (PUR) plasticity were investigated in rats, which received a sham operation (Sham), ovariectomy (OVX), or ovariectomy with daily supplemental estrogen (50 g/kg, OVX ؉ E 2 ). The magnitude of the repetitive stimulation (RS, 1 Hz)-induced potentiation in PUR activity decreased significantly in the OVX group when compared with the Sham groups (18.09 ؎ 3.91 and 7.40 ؎ 1.03 spikes/stimulation in Sham and OVX group; respectively, P < 0.01, n ‫؍‬ 21). Supplemental estrogen (OVX ؉ E 2 , 12.60 ؎ 1.49 spikes/stimulation) significantly reversed the decrease in RS-induced PUR potentiation caused by OVX (P < 0.01, n ‫؍‬ 21). The magnitude of the RSinduced potentiation in PUR activity decreased significantly after intrathecal 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo F) quinoxaline [(20 M, 10 l), from 18.09 ؎ 3.91 to 10.40 ؎ 0.81, from 7.40 ؎ 1.03 to 3.20 ؎ 0.94, and from 12.60 ؎ 1.49 to 8.06 ؎ 0.32 spikes/stimulation in Sham, OVX, and OVX ؉ E 2 , respectively, P < 0.01, n ‫؍‬ 18] and D -2-amino-5-phosphonoraleric acid [(100 M, 10 l), from 18.09 ؎ 3.91 to 1.04 ؎ 0.12, from 7.40 ؎ 1.03 to 1.06 ؎ 0.22, and from 12.60 ؎ 1.49 to 0.98 ؎ 0.25 spikes/ stimulation in Sham, OVX, and OVX ؉ E 2 , respectively, P < 0.01, n ‫؍‬ 18]. In addition, potentiation in PUR activities was induced by intrathecal L-glutamate (0.1 mM, 10 l, from 1.04 ؎ 0.02 to 21.60 ؎ 0.93, from 1.10 ؎ 0.06 to 8.40 ؎ 1.50, and from 1.03 ؎ 0.03 to 18.04 ؎ 0.84 spikes/stimulation in Sham, OVX, and OVX ؉ E 2 , respectively, P < 0.01, n ‫؍‬ 18) and N-methyl-Daspartic acid (0.1 mM, 10 l, from 1.04 ؎ 0.02 to 14.80 ؎ 0.97, from 1.10 ؎ 0.06 to 4.60 ؎ 0.48, and from 1.03 ؎ 0.03 to 9.09 ؎ 0.63 spikes/stimulation in Sham, OVX, and OVX ؉ E 2 ); N-methyl-D-aspartic acid-mediated PUR plasticity in female rats and may contribute to alterations in urinary dysfunction after menopause.