scholarly journals Effect of a 5-HT1A receptor agonist (8-OH-DPAT) on external urethral sphincter activity in a rat model of pudendal nerve injury

2011 ◽  
Vol 301 (1) ◽  
pp. R225-R235 ◽  
Author(s):  
Shih-Ching Chen ◽  
Chen-Li Cheng ◽  
Wen-Jia Fan ◽  
Jia-Jin Jason Chen ◽  
Chien-Hung Lai ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Rat Model ◽  
Receptor Agonist ◽  
Pudendal Nerve ◽  
Perfusion Pressure ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Point Pressure ◽  
Pudendal Nerve Injury

Although serotonergic agents have been used to treat patients with stress urinary incontinence, the characteristics of the external urethral sphincter (EUS) activity activated by 5-HT receptors have not been extensively studied. This study examined the effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), on the EUS-electromyography and resistance of the urethra in a rat model with bilateral pudendal nerve injury (BPNI). Two measurements were utilized to assess the effects of the drug on bladder and urethral functions: the simultaneous recordings of transvesical pressure under isovolumetric conditions [isovolumetric intravesical pressure (IVP)] and urethral perfusion pressure, and the simultaneous recordings of IVP during continuously isotonic transvesical infusion with an open urethra (isotonic IVP) and EUS-electromyography. This study also evaluated the urethral continence using leak point pressure testing. The urethral perfusion pressure and leak point pressure measurements of BPNI rats reveal that 8-OH-DPAT significantly increased urethral resistance during the bladder storage phase, yet decreased resistance during the voiding phase. The entire EUS burst period was significantly prolonged, within which the average silent period increased and the frequency of burst discharges decreased. 8-OH-DPAT also improved the voiding efficiency, as evidenced by the detection of decreases in the contraction amplitude and residual volume, with increases in contraction duration and voided volume. These findings suggest that 8-OH-DPAT not only improved continence function, but also elevated the voiding function in a BPNI rat model.

External urethral sphincter activity in a rat model of pudendal nerve injury

2006 ◽  
Vol 25 (4) ◽  
pp. 388-396 ◽  
Author(s):  
Chih-Wei Peng ◽  
Jia-Jin Jason Chen ◽  
Hui-Yi Chang ◽  
William C. de Groat ◽  
Chen-Li Cheng
Keyword(s):  
Nerve Injury ◽  
Rat Model ◽  
Pudendal Nerve ◽  
Urethral Sphincter ◽  
External Urethral Sphincter ◽  
Pudendal Nerve Injury

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat

2013 ◽  
Vol 305 (9) ◽  
pp. F1332-F1342 ◽  
Author(s):  
Wen-Jia Fan ◽  
Yu-Ting Li ◽  
Jia-Jin Jason Chen ◽  
Shih-Ching Chen ◽  
You Shuei Lin ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Sexual Differences ◽  
Female Rats ◽  
Male Rats ◽  
Sexually Dimorphic ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Sphincter Electromyography ◽  
Point Pressure

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men.

scholarly journals Pudendal nerve injury reduces urethral outlet resistance in diabetic rats

2010 ◽  
Vol 299 (6) ◽  
pp. F1443-F1450 ◽  
Author(s):  
Hui Q. Pan ◽  
Dan L. Lin ◽  
Christopher Strauch ◽  
Robert S. Butler ◽  
Vincent M. Monnier ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Pudendal Nerve ◽  
Outlet Obstruction ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
External Urethral Sphincter ◽  
Nerve Crush ◽  
Point Pressure ◽  
Functional Outlet Obstruction ◽  
Pudendal Nerve Injury

Diabetics have voiding and continence dysfunction to which elevated levels of advanced glycation end products (AGE) may contribute. In addition, pudendal nerve injury is correlated with voiding dysfunction and stress incontinence in rats. The aim of this study was to investigate whether pudendal nerve crush (PNC) in diabetic rats alters urinary function. Female virgin Sprague-Dawley rats (144) were divided equally into diabetic, diuretic, and control groups. Half of the animals in each group were subjected to PNC, and the other half to sham PNC. Diabetes was induced 8 wk before PNC or sham PNC by streptozotocin injection (35 mg/kg). Animals underwent conscious cystometry and leak point pressure (LPP) testing 4 or 13 days after PNC or sham PNC. Tissues of half the animals were tested for levels of AGEs. Qualitative histological assessment was performed in the remaining animals. Diabetic rats 4 days after PNC voided significantly greater volume in a shorter time and with significantly less pressure than after sham PNC, suggesting that diabetic rats have a functional outlet obstruction that is relieved by PNC. LPP was significantly reduced 4 days after PNC in diabetic and diuretic animals and returned to normal 13 days after PNC. Diabetic rats with PNC demonstrated increased muscle fiber disruption and atrophy of the external urethral sphincter. AGEs were significantly elevated in diabetic rats. PNC relieves a functional outlet obstruction in diabetic rats. AGEs are elevated in diabetic rats and could play a role in urinary dysfunction and recovery from PNC.

scholarly journals Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis and Facilitates Recovery from Simulated Childbirth Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1395-1406 ◽  
Author(s):  
Charuspong Dissaranan ◽  
Michelle A. Cruz ◽  
Matthew J. Kiedrowski ◽  
Brian M. Balog ◽  
Bradley C. Gill ◽  
...  
Keyword(s):  
Female Rats ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Paracrine Factors ◽  
Pelvic Organs ◽  
Point Pressure ◽  
Urethral Smooth Muscle ◽  
And Function ◽  
Vaginal Distension

Vaginal delivery is a risk factor for stress urinary incontinence (SUI). Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair. The goal of this study was to determine if MSCs home to pelvic organs after simulated childbirth injury and facilitate recovery from SUI via paracrine factors. Three experiments were performed. Eighteen female rats received vaginal distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of continence. Twenty-nine female rats received VD and periurethral concentrated conditioned media (CCM), VD and periurethral control media, or sham VD and periurethral control media to investigate if factors secreted by MSCs accelerate recovery from VD. Urethral histology and function were assessed 1 week later. Significantly more MSCs were observed in the urethra, vagina, and spleen after VD compared to sham VD. Continence as measured by leak point pressure (LPP) was significantly reduced after VD in rats treated with saline or control media compared to sham VD but not in those given MSCs or CCM. External urethral sphincter (EUS) function as measured by electromyography (EMG) was not improved with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in elastin fibers near the EUS and urethral smooth muscle more similar to that of sham-injured animals than rats treated with saline or control media. MSCs homed to the urethra and vagina and facilitated recovery of continence most likely via secretion of paracrine factors. Both MSCs and CCM have promise as novel noninvasive therapies for SUI.

Validation of a new rat model of urethral sphincter injury and leak point pressure measurements

2021 ◽  
pp. 1-7
Author(s):  
Abdelkhalek Samy Abdelkhalek ◽  
Patrick D. Clarke ◽  
Matthew A. Sommers ◽  
Tyler Oe ◽  
Thomas M. Andersen ◽  
...  
Keyword(s):  
Rat Model ◽  
Pressure Measurements ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
Sphincter Injury ◽  
Point Pressure

scholarly journals Electrical stimulation of the pudendal nerve promotes neuroregeneration and functional recovery from stress urinary incontinence in a rat model

2018 ◽  
Vol 315 (6) ◽  
pp. F1555-F1564 ◽  
Author(s):  
Hai-Hong Jiang ◽  
Qi-Xiang Song ◽  
Bradley C. Gill ◽  
Brian M. Balog ◽  
Raul Juarez ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Electrical Stimulation ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Pudendal Nerve ◽  
External Urethral Sphincter ◽  
Sham Stimulation ◽  
Point Pressure ◽  
Separate Cohort ◽  
Stimulation Of

The pudendal nerve can be injured during vaginal delivery of children, and slowed pudendal nerve regeneration has been correlated with development of stress urinary incontinence (SUI). Simultaneous injury to the pudendal nerve and its target muscle, the external urethral sphincter (EUS), during delivery likely leads to slowed neuroregeneration. The goal of this study was to determine if repeat electrical stimulation of the pudendal nerve improves SUI recovery and promotes neuroregeneration in a dual muscle and nerve injury rat model of SUI. Rats received electrical stimulation or sham stimulation of the pudendal nerve twice weekly for up to 2 wk after injury. A separate cohort of rats received sham injury and sham stimulation. Expression of brain-derived neurotrophic factor (BDNF) and βII-tubulin expression in Onuf’s nucleus were measured 2, 7, and 14 days after injury. Urodynamics, leak point pressure (LPP), and EUS electromyography (EMG) were recorded 14 days after injury. Electrical stimulation significantly increased expression of BDNF at all time points and βII-tubulin 1 and 2 wk after injury. Two weeks after injury, LPP and EUS EMG during voiding and LPP testing were significantly decreased compared with sham-injured animals. Electrical stimulation significantly increased EUS activity during voiding, although LPP did not fully recover. Repeat pudendal nerve stimulation promotes neuromuscular continence mechanism recovery possibly via a neuroregenerative response through BDNF upregulation in the pudendal motoneurons in this model of SUI. Electrical stimulation of the pudendal nerve may therefore improve recovery after childbirth and ameliorate symptoms of SUI by promoting neuroregeneration after injury.

scholarly journals Dual simulated childbirth injury delays anatomic recovery

2009 ◽  
Vol 296 (2) ◽  
pp. F277-F283 ◽  
Author(s):  
Hui Q. Pan ◽  
James M. Kerns ◽  
Dan L. Lin ◽  
David Sypert ◽  
James Steward ◽  
...  
Keyword(s):  
Pudendal Nerve ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Bdnf Expression ◽  
Nerve Crush ◽  
Histological Evidence ◽  
Injury Model ◽  
Point Pressure ◽  
Urethral Function ◽  
Vaginal Distension

A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.

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