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1.
Urology ; 137: 183-189, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926195

RESUMO

OBJECTIVE: To characterize the bulbospongiosus muscle (BSM) in patients with bulbar urethral strictures. MATERIALS AND METHODS: We studied 21 patients divided into 2 groups: Stricture Group (n = 14; mean age = 62.00 years) with bulbar stricture submitted to open urethroplasty; and Control Group (n = 7; mean age = 60.14 years) with penile strictures (hypospadias cripples, penile cancer and/or penile infection) who were submitted to perineal urethrostomy. Samples of the BSM were dissected and histologic sections were stained by histochemical and immunohistochemical techniques. Histomorphometric analyzes were performed on photomicrographs. Means were statistically compared using the unpaired Student t test and the Mann-Whitney test (P <.05). RESULTS: The etiology of bulbar urethral stricture was idiopathic in 2 cases (14.29%), post-TURP in 6 (42.86%), post open radical prostatectomy in 5 (35.71%) and post open prostatectomy in 1 case (7.14%). The average length of the stricture was 2.08 cm. The only parameter analyzed with significant difference between the groups was the vessels (significant difference between the control group: 5.11 ± 1.98% and stricture group: 3.57 ± 1.32%, P = .0460). The quantitative analysis of collagen (Control Group: 10.63 ± 5.37% and Stricture Group: 10.83 ± 4.55%, P = .9296); diameter of BSM muscle fibers (Control Group: 41.71 ± 14.63 µm and Stricture Group: 40.11 ± 8.59 µm, P = .76 and elastic system fibers (Control Group; 3.83 ± 1.54% and Stricture Group: 5.43 ± 2.90%, P = .2601) showed no significant difference. CONCLUSIONS: Histologic analysis showed a significant decrease of the BSM vessels in urethral stricture, without changes in elastic fibers, collagen, nerves, and muscle fiber diameter. These findings show that the bulbar urethral stricture causes minimal alterations in the structure of the BSM.


Assuntos
Doenças do Pênis , Pênis , Complicações Pós-Operatórias , Uretra , Estreitamento Uretral , Procedimentos Cirúrgicos Urológicos , Pesos e Medidas Corporais/métodos , Brasil , Constrição Patológica , Correlação de Dados , Técnicas de Imagem por Elasticidade/métodos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Doenças do Pênis/diagnóstico , Doenças do Pênis/etiologia , Pênis/patologia , Pênis/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Uretra/irrigação sanguínea , Uretra/inervação , Uretra/patologia , Uretra/cirurgia , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/epidemiologia , Estreitamento Uretral/etiologia , Estreitamento Uretral/patologia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Procedimentos Cirúrgicos Urológicos/métodos
2.
J Pharmacol Sci ; 139(4): 333-339, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871873

RESUMO

The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT2C receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT2C receptor, with an EC50 of 0.85 nM in the intracellular Ca2+ mobilization assay. Rat 5-HT2C receptor was also activated by ASP2205 with an EC50 of 2.5 nM. Intraduodenal administration (i.d.) of ASP2205 (0.1-1 mg/kg) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner. This ASP2205 (0.3 mg/kg i.d.)-induced LPP elevation was inhibited by SB242084 (0.3 mg/kg i.v.), a selective 5-HT2C receptor antagonist. Urethral closure responses induced by intravesical pressure loading in rats were enhanced by ASP2205 (0.3 mg/kg i.v.), which was abolished by pretreatment with SB242084 (0.3 mg/kg i.v.) and bilateral transection of the pudendal nerve. In contrast, ASP2205 (0.3 mg/kg i.v.) did not change the resting urethral pressure in rats. These results indicate that ASP2205 can enhance the pudendal nerve-mediated urethral closure reflex via the 5-HT2C receptor, resulting in the prevention of involuntary urine loss.


Assuntos
Fumaratos/farmacologia , Pressão , Reflexo/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Uretra/fisiologia , Animais , Azepinas , Relação Dose-Resposta a Droga , Feminino , Fumaratos/uso terapêutico , Quinolinas , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Uretra/inervação , Uretra/fisiopatologia , Incontinência Urinária por Estresse/prevenção & controle
3.
Neurourol Urodyn ; 38(3): 893-901, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30779374

RESUMO

AIMS: To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. METHODS: Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. RESULTS: The female rat urethra is not a homogeneous tubular organ. The pre-pelvic and pelvic regions are firmly attached to the vagina with belt-like striated fibers forming a urethra-vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra-clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). CONCLUSIONS: Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra-vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra-clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.


Assuntos
Uretra/metabolismo , Uretra/fisiologia , Incontinência Urinária , Micção/fisiologia , Acetilcolinesterase/metabolismo , Animais , Composição Corporal , Clitóris/anatomia & histologia , Clitóris/inervação , Clitóris/fisiologia , Feminino , Plexo Hipogástrico/fisiologia , Plexo Lombossacral/fisiologia , Nervo Pudendo/fisiologia , Ratos , Ratos Wistar , Uretra/inervação , Vagina/anatomia & histologia , Vagina/inervação , Vagina/fisiologia
4.
Low Urin Tract Symptoms ; 11(2): O21-O27, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29105998

RESUMO

OBJECTIVE: The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO). METHODS: The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO-negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO-negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2 O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square-wave stimulation at 3 Hz to activate C-fiber afferents. RESULTS: Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non-UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO-positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11). CONCLUSION: Hyposensitive C-fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.


Assuntos
Fibras Nervosas Amielínicas/fisiologia , Uretra/inervação , Bexiga Urinária Hiperativa/complicações , Incontinência Urinária de Urgência/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Uretra/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária de Urgência/fisiopatologia , Urodinâmica , Adulto Jovem
5.
Low Urin Tract Symptoms ; 11(2): O186-O192, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29266769

RESUMO

OBJECTIVE: Stress urinary incontinence (SUI) is a common disease condition in elderly women, suggesting that its etiology may be linked to aging. To investigate the hypothesis that urethral dysfunction and histopathological changes are possible contributors to SUI in elderly women, several parameters of urethral function, as well as histological parameters, were compared between young and aged rats. METHODS: Virgin female rats were examined at 3 different ages, namely 3, 12, and 24 months, corresponding to young, middle-aged, and aged rats, respectively. Urethral function was assessed by measuring the leak point pressure (LPP), pudendal nerve stimulation (PNS)-induced elevation in urethral pressure, and phenylephrine-induced increase in urethral perfusion pressure (UPP). Histopathological assessments were performed following hematoxylin and eosin (HE), Masson's trichrome, and immunofluorescence staining of urethral tissue. RESULTS: LPP of aged rats was significantly reduced compared to that of both young and middle-aged rats. PNS-induced elevation in urethral pressure in aged rats was also significantly lower than that in young rats. In contrast, there were no significant differences in the phenylephrine-induced increase in UPP between young and aged rats. Connective tissue area in the external urethral sphincter (EUS) layer was increased in aged rats, whereas the smooth muscle layer was histologically similar to that in young rats. The number of EUS fibers was significantly reduced in aged rats, whereas the cross-sectional area of EUS fibers increased from differed compared with young rats. CONCLUSION: We have demonstrated age-related changes in EUS function and morphology in the rat urethra, which are considered to be etiological risk factors for SUI in humans.


Assuntos
Modelos Animais de Doenças , Uretra/fisiopatologia , Incontinência Urinária por Estresse/fisiopatologia , Envelhecimento , Animais , Feminino , Imunofluorescência , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Uretra/patologia , Incontinência Urinária por Estresse/etiologia
7.
Nat Neurosci ; 21(9): 1229-1238, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30104734

RESUMO

Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington's nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (BarESR1), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.


Assuntos
Tronco Encefálico/fisiologia , Neurônios/fisiologia , Uretra/inervação , Uretra/fisiologia , Micção/fisiologia , Animais , Tronco Encefálico/citologia , Eletromiografia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/fisiologia , Masculino , Camundongos , Vias Neurais/fisiologia , Odorantes , Optogenética , Transtornos Urinários/genética , Transtornos Urinários/fisiopatologia
8.
Neurourol Urodyn ; 37(8): 2614-2624, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29717501

RESUMO

AIMS: To assess the afferent innervation of various locations in the male lower urinary tract (LUT) using sensory evoked cortical potentials (SEPs). METHODS: Twelve healthy men (mean age: 29.6 ± 7.2 years, mean height: 1.8 ± 0.1 m) underwent repetitive slow (0.5 Hz/1 ms) and fast (3 Hz/0.2 ms) electrical stimulations of bladder (dome/trigone) and urethral (proximal/membranous/distal) locations with simultaneous cortical SEP recording (Cz-Fz). Latencies (ms) and peak-to-peak amplitudes (µV) for SEP components P1, N1, and P2 were analyzed. Tibial SEPs were assessed as methodological control. The reproducibility was investigated from between visits and inter-rater assessments using Bland-Altman plots. Statistical tests comprised analysis of variance (ANOVA), linear regressions, and paired t-tests. Values are given as mean ± standard deviation. RESULTS: Typical LUTSEPs with P1, N1, and P2 components were successfully detected (100% responder rate) for slow but less successfully for fast stimulation. The slow stimulation provided reproducible LUTSEPs with position specific N1 latencies: dome 125.6 ± 21.3 ms, trigone 122.9 ± 20.5 ms, proximal- 116.1 ± 21.4 ms, membraneous- 118.8 ± 29.3 ms, and distal urethra 108.8 ± 17.8 ms. Despite good inter-rater agreement, latency variability between and within subjects was higher for LUTSEPs than for tibial SEPs. N1 latencies became shorter (P < 0.01) with increasing subject age for bladder dome and distal urethra stimulation. CONCLUSIONS: LUTSEPs can be successfully obtained for different LUT locations in men using slow electrical stimulation. Location specific differences in N1 latencies may indicate different local afferent innervation. Larger variability of LUTSEPs versus tibial SEPs may be related to the more challenging approach and afferent fibre access within the LUT. Further studies optimizing measurement and analysis approach are required.


Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Uretra/fisiologia , Bexiga Urinária/fisiologia , Adulto , Análise de Variância , Estimulação Elétrica , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos Testes , Uretra/inervação , Bexiga Urinária/inervação , Adulto Jovem
9.
Neurourol Urodyn ; 37(8): 2389-2397, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29664149

RESUMO

AIM: To study the contribution of urethral serotonin for the urethro-vesical crosstalk METHODS: Urethane-anesthetized female rats and TPH1-/- mice underwent isovolumetric or urethral-opened cystometries during intravesical or intraurethral infusion of saline or serotonin solutions. Human and rat bladders and urethrae were immunoreacted against serotonin and neuronal markers. Serotonin concentration and TPH1 mRNA were determined in rat tissue by HPLC and qPCR. RESULTS: In rats, under isovolumetric conditions, intraurethral serotonin infusion, but not saline, evoked bladder contractions. This was abolished by urethral anesthesia and by treatment with serotonin receptor antagonists. Serotonin infusion into the bladder had no effect. Under urethral-opened conditions, serotonin infusion reduced the frequency and increased the amplitude of reflex voiding contractions, compared to saline infusion. TPH1-/- mice, under urethral-opened conditions, exhibited increased frequency and reduced amplitude of voiding contractions compared to WT. Serotonin concentration and TPH1 mRNA expression were higher in the urethra than in the bladder. Cells 5-HT+ were found in the human and rat urethral epithelium, close to a sub-epithelial network of cholinergic and sensory fibers, but not in the bladder. CONCLUSIONS: Serotonin, produced and released by urethral cells activates an urethro-vesical pathway that enhances bladder reflex contractions.


Assuntos
Serotonina/fisiologia , Uretra/fisiologia , Bexiga Urinária/fisiologia , Adulto , Anestesia , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Reflexo/efeitos dos fármacos , Serotonina/metabolismo , Serotonina/farmacologia , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/fisiologia , Uretra/inervação , Uretra/metabolismo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação , Micção/efeitos dos fármacos
10.
Exp Neurol ; 305: 26-32, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29530711

RESUMO

Spinal cord epidural stimulation (SCS) represents a form of neuromodulation for the management of spasticity and pain. This technology has recently emerged as a new approach for potentially augmenting locomotion and voiding function in humans and rodents after spinal cord injury. However, the effect of SCS on micturition has not been studied extensively. Here, SCS was first applied as a direct stimulus onto individual segmental levels of the lumbar spinal cord in rats to map evoked external urethral sphincter (EUS) electromyography activity and SCS-induced voiding contractions. SCS of L2-3 inhibited EUS tonic activity, and SCS on L3 (L3/SCS) inhibited EUS tonic activity and elicited EUS bursting. In contrast, SCS of L1 and L4-6 evoked EUS tonic contractions, which resembled the urethral guarding reflex during bladder storage. Next, the effects of a bilateral pelvic nerve crush (PNC) injury on urodynamic function were examined at 14 days post-operatively. The PNC injury resulted in decreased voiding efficiency and maximum intravesical pressure, whereas the post-voiding residual volume was increased, suggestive of an underactive bladder. Finally, L3/SCS was performed to induce a voiding contraction and enable voiding in rats with a PNC injury. Voiding efficiency was significantly increased, and the residual volume was decreased by L3/SCS in rats after the PNC injury. We conclude that L3/SCS may be used to induce micturition reflexes in a partially filled bladder, reduce urethral resistance, and augment bladder emptying after PNC injury.


Assuntos
Estimulação da Medula Espinal/métodos , Medula Espinal/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Uretra/fisiologia , Bexiga Urinária/fisiologia , Micção/fisiologia , Animais , Feminino , Vértebras Lombares/inervação , Vértebras Lombares/fisiologia , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Bexiga Urinária/inervação
11.
Clin Anat ; 31(6): 788-796, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29577446

RESUMO

The aim of this study was to investigate the nerve supply to the structures in the male lesser pelvis and review its clinical relevance, especially during nerve sparing surgery. Three formalin-embalmed and 16 Thiel-embalmed male hemipelves were used. They were microdissected after repeated treatments with nitric acid diluted 1:10 with milliQ-water. The inferior hypogastric plexus (IHP) is a fan-like structure lateral from the rectum on the fascia of the levator ani. Nerves emerging from the proximal, solid part of the plexus follow the internal iliacal vessels and reach the prostate from dorsolateral. The innervation of the urethra and the corpora cavernosa derives from two origins: one follows the ejaculatory duct and the seminal vesicle, reaching the proximal urethra and the prostate from dorsal; the other follows the inferior vesical artery to reach the prostate from lateral, and then forms the neurovascular bundle on both sides of the prostatic fascia, spreading to the pelvic floor muscles and the corpora cavernosa along with the distal urethra. A connection between the two parts was demonstrated in approximately one third of the samples investigated. The nerve supply to the urinary bladder, the urethra, and the corpora cavernosa emerges mainly from the IHP. The innervation of the proximal urethra and its autonomic muscular structures has a dorsal (ejaculatory duct) and lateral (inferior vesical artery) origin. To maintain good erectile and continence function it is important to save both the dorsal and lateral neurovascular roots. Clin. Anat. 31:788-796, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Plexo Hipogástrico/anatomia & histologia , Tratamentos com Preservação do Órgão , Ereção Peniana/fisiologia , Cadáver , Dissecação , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Diafragma da Pelve/inervação , Pelve/inervação , Próstata/inervação , Glândulas Seminais/inervação , Uretra/inervação , Bexiga Urinária/inervação
12.
Anat Rec (Hoboken) ; 301(8): 1426-1441, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29575690

RESUMO

Many studies examining the innervation of genitourinary structures focus on either afferent or efferent inputs, or on only one structure of the system. We aimed to clarify innervation of the bladder, external urethral sphincter (EUS) and clitoris. Retrograde dyes were injected into each end organ in female dogs. Spinal cord, mid-bladder, and spinal, caudal mesenteric, sympathetic trunk and pelvic plexus ganglia were examined for retrograde dye-labeled neurons. Neurons retrogradely labeled from the bladder were found primarily in L7-S2 spinal ganglia, spinal cord lateral zona intermedia at S1-S3 levels, caudal mesenteric ganglia, T11-L2 and L6-S2 sympathetic trunk ganglia, and pelvic plexus ganglia. The mid-bladder wall contained many intramural ganglia neurons labeled anterogradely from the pelvic nerve, and intramural ganglia retrogradely labeled from dye labeling sites surrounding ureteral orifices. Neurons retrogradely labeled from the clitoris were found only in L7 and S1 spinal ganglia, L7-S3 spinal cord lateral zona intermedia, and S1 sympathetic trunk ganglia, and caudal mesenteric ganglia. Neurons retrogradely labeled from the EUS were found in primarily at S1 and S2 spinal ganglia, spinal cord lamina IX at S1-S3, caudal mesenteric ganglia, and S1-S2 sympathetic trunk ganglia. Thus, direct inputs from the spinal cord to each end organ were identified, as well as multisynaptic circuits involving several ganglia, including intramural ganglia in the bladder wall. Knowledge of this complex circuitry of afferent and efferent inputs to genitourinary structures is necessary to understand and treat genitourinary dysfunction. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Clitóris/inervação , Neurônios , Nervos Espinhais , Uretra/inervação , Bexiga Urinária/inervação , Animais , Clitóris/química , Clitóris/citologia , Corantes/administração & dosagem , Cães , Feminino , Neurônios/química , Nervos Espinhais/química , Nervos Espinhais/citologia , Coloração e Rotulagem/métodos , Uretra/química , Uretra/citologia , Bexiga Urinária/química , Bexiga Urinária/citologia
13.
Am J Physiol Renal Physiol ; 315(1): F79-F85, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442547

RESUMO

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.


Assuntos
Reflexo , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Espirro , Uretra/inervação , Incontinência Urinária por Estresse/etiologia , Animais , Modelos Animais de Doenças , Feminino , Fenclonina/farmacologia , Piperazinas/farmacologia , Pressão , Pirazinas/farmacologia , Ratos Sprague-Dawley , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Incontinência Urinária por Estresse/metabolismo , Incontinência Urinária por Estresse/fisiopatologia , Incontinência Urinária por Estresse/prevenção & controle
14.
Int J Neurosci ; 128(7): 663-669, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29199538

RESUMO

AIM: The morphologic mechanism of orgasmic sensation has not yet been understood. Taste roseas may be stimulated by fructose via pudendal nerves, which has not been studied yet. METHODS: In this study, 27 male adult rabbits were used, which were divided into three groups: 5 as control; 5 as SHAM and 17 used as study group. We injected 0.2 cc of distilled water to SHAM and 0.2 cc of fructose solution to the study group of their urethral orifices, and examined the occurrence of penile erection. The relationship between erection and pudendal nerve ganglia and penile tissues was statistically compared. RESULTS: In animals with high neuron density of pudendal ganglia, more erection phenomenon was observed than those animals with low neuron density. Interestingly, neuron density of pudendal ganglia was 9.243 ± 542 /mm3 in hypoactive and was 5.980 ± 463 /mm3 in non-active animals (p < 0.05). CONCLUSIONS: The seminal fructose may stimulate taste roseas of the urethra and glans penis via pudendal nerves. The present study describes a new neuro-morpho-chemical mechanism of orgasmic sensation with its neurosurgical aspect.


Assuntos
Ereção Peniana/fisiologia , Pênis/citologia , Células Receptoras Sensoriais/fisiologia , Paladar/fisiologia , Uretra/fisiologia , Animais , Modelos Animais de Doenças , Frutose/farmacologia , Gânglios Espinais/citologia , Masculino , Coelhos , Células Receptoras Sensoriais/efeitos dos fármacos , Língua/citologia , Uretra/inervação
15.
Am J Physiol Regul Integr Comp Physiol ; 314(1): R34-R42, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28931549

RESUMO

This study tested the hypothesis that sacral neuromodulation, i.e., electrical stimulation of afferent axons in sacral spinal root, can block pudendal afferent inhibition of the micturition reflex. In α-chloralose-anesthetized cats, pudendal nerve stimulation (PNS) at 3-5 Hz was used to inhibit bladder reflex activity while the sacral S1 or S2 dorsal root was stimulated at 15-30 Hz to mimic sacral neuromodulation and to block the bladder inhibition induced by PNS. The intensity threshold (T) for PNS or S1/S2 dorsal root stimulation (DRS) to induce muscle twitch of anal sphincter or toe was determined. PNS at 1.5-2T intensity inhibited the micturition reflex by significantly ( P < 0.01) increasing bladder capacity to 150-170% of control capacity. S1 DRS alone at 1-1.5T intensity did not inhibit bladder activity but completely blocked PNS inhibition and restored bladder capacity to control level. At higher intensity (1.5-2T), S1 DRS alone inhibited the micturition reflex and significantly increased bladder capacity to 135.8 ± 6.6% of control capacity. However, the same higher intensity S1 DRS applied simultaneously with PNS, suppressed PNS inhibition and significantly ( P < 0.01) reduced bladder capacity to 126.8 ± 9.7% of control capacity. S2 DRS at both low (1T) and high (1.5-2T) intensity failed to significantly reduce PNS inhibition. PNS and S1 DRS did not change the amplitude and duration of micturition reflex contractions, but S2 DRS at 1.5-2T intensity doubled the duration of the contractions and increased bladder capacity. These results are important for understanding the mechanisms underlying sacral neuromodulation of nonobstructive urinary retention in Fowler's syndrome.


Assuntos
Plexo Lombossacral , Inibição Neural , Nervo Pudendo/fisiopatologia , Reflexo , Estimulação Elétrica Nervosa Transcutânea/métodos , Bexiga Urinária/inervação , Retenção Urinária/terapia , Micção , Animais , Gatos , Modelos Animais de Doenças , Feminino , Masculino , Diafragma da Pelve/inervação , Síndrome , Uretra/inervação , Retenção Urinária/etiologia , Retenção Urinária/fisiopatologia , Urodinâmica
16.
Neurourol Urodyn ; 37(3): 960-970, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29053899

RESUMO

BACKGROUND: Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented. AIMS: To determine the distribution and projection sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild-type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice. Furthermore, to identify the location and neurochemical coding of the spinal afferent nerve endings in the urethra, whose sensory neurons reside in lumbosacral dorsal root ganglia (DRG). METHODS: Multiple labeling immunohistochemistry of urethral sections of nulliparous (6-8 weeks old), and multiparous (9-12 months old) mice, and anterograde axonal tracing from L5-S2 (DRG) in vivo. RESULTS: Abundant VIP-, CGRP-, SP-, and NPY-immunoreactive nerve fibers were identified in the adventitia, muscularis, and lamina propria of proximal and distal segments of the urethra. A proportion of fibers were closely associated with blood vessels, glands, and cells immunoreactive for PGP9.5. The epithelium contained abundant nerve fibers immunoreactive for CGRP and/or SP. Epithelial innervation was increased in the distal urethra of multipara mice. Abundant fibers were traced from L5-S2 DRG to all urethral regions. CONCLUSIONS: We present the first identification of spinal afferent endings in the urethra. Peptidergic nerve fibers, including multiple populations of spinal afferents, provide rich innervation of the female mouse urethra. The morphology of fibers in the epithelium and other regions suggests multiple nerve-cell interactions impacting on urethral function.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fibras Nervosas/metabolismo , Neuropeptídeo Y/metabolismo , Substância P/metabolismo , Uretra/inervação , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Feminino , Gânglios Espinais/metabolismo , Imuno-Histoquímica , Camundongos , Uretra/metabolismo
17.
Acta Physiol (Oxf) ; 222(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28719042

RESUMO

AIM: The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here, we examined the morphology and potential role in sensory signalling of a different class of specialized cells that express serotonin (5-HT), termed paraneurones. METHODS: Urethrae, dorsal root ganglia neurones and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging. Visceromotor reflexes (VMRs) were recorded in vivo. RESULTS: We identified two morphologically distinct groups of 5-HT+ cells with distinct regional locations: bipolar-like cells predominant in the mid-urethra and multipolar-like cells predominant in the proximal and distal urethra. Sensory nerve fibres positive for calcitonin gene-related peptide, substance P, and TRPV1 were found in close proximity to 5-HT+ paraneurones. In vitro 5-HT (1 µm) stimulation of urethral primary afferent neurones, mimicking 5-HT release from paraneurones, elicited changes in the intracellular calcium concentration ([Ca2+ ]i ) mediated by 5-HT2 and 5-HT3 receptors. Approximately 50% of 5-HT responding cells also responded to capsaicin with changes in the [Ca2+ ]i . In vivo intra-urethral 5-HT application increased VMRs induced by urethral distention and activated pERK in lumbosacral spinal cord neurones. CONCLUSION: These morphological and functional findings provide insights into a putative paraneurone-neural network within the urethra that utilizes 5-HT signalling, presumably from paraneurones, to modulate primary sensory pathways carrying nociceptive and non-nociceptive (mechano-sensitive) information to the central nervous system.


Assuntos
Vias Aferentes/citologia , Células Quimiorreceptoras/citologia , Células Quimiorreceptoras/metabolismo , Células Epiteliais/citologia , Uretra/citologia , Animais , Feminino , Camundongos , Serotonina/metabolismo , Uretra/inervação
18.
J Am Vet Med Assoc ; 251(7): 818-823, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28967822

RESUMO

CASE DESCRIPTION A 15-year-old spayed female mixed-breed dog was evaluated for a 7-week history of stranguria, pollakiuria, and intermittent urethral obstruction. CLINICAL FINDINGS On initial evaluation, the patient had persistent stranguria with lack of urine production; after multiple unsuccessful attempts to urinate, a large volume of urine was produced. Prior to voiding the large volume, the urinary bladder was not palpable during examination. Abdominal ultrasonography confirmed caudal displacement of the urinary bladder, and the urethra and trigone could not be located ultrasonographically. Positive-contrast cystourethrography and CT confirmed caudal displacement of the urinary bladder and also revealed trigonal invagination and urethral kinking; dysuria was attributed to these findings. TREATMENT AND OUTCOME Surgical repositioning of the lower urinary tract was performed. The urinary bladder was moved cranially and was fixed in place along the left lateral aspect of the body wall by cystopexy. After surgery, positive-contrast cystourethrography revealed a more cranial positioning of the urinary bladder and straightening of the urethra with no urethral kinking or trigonal invagination. Immediately after surgery, stranguria had resolved and the patient was able to void normally. Two years after surgery, the dog was reported to be urinating normally. CLINICAL RELEVANCE Surgical correction of caudal urinary bladder displacement with cystopexy led to resolution of trigonal invagination, urethral kinking, and urethral obstruction in the dog of the present report. Trigonal invagination and urethral kinking, although uncommon findings, should be considered as possible causes of dysuria in dogs.


Assuntos
Doenças do Cão/cirurgia , Uretra/anormalidades , Obstrução Uretral/veterinária , Bexiga Urinária , Animais , Cães , Disuria , Feminino , Uretra/inervação , Obstrução Uretral/cirurgia
19.
Urology ; 109: 210-215, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28801220

RESUMO

OBJECTIVE: To measure the urodynamic effects of electrical co-stimulation of 2 individual sites in the proximal and distal urethra in persons with spinal cord injury (SCI). This work was motivated by preclinical findings that selective co-stimulation of the cranial urethral sensory nerve and the dorsal genital nerve, which innervate the proximal and distal portions of the urethra, respectively, increased reflex bladder activation and voiding efficiency. MATERIALS AND METHODS: Electrical co-stimulation of urethral afferents was conducted in persons with chronic SCI during urodynamics. The effects of different frequencies of intraurethral stimulation at multiple urethral locations on bladder pressure and pelvic floor electromyographic activity were measured. RESULTS: Electromyographic activity indicated that multiple reflex pathways were recruited through stimulation that contributed to bladder activation. The size of reflex bladder contractions evoked by stimulation was dependent on stimulation location or reflex activated and stimulation frequency. CONCLUSION: Pudendal nerve afferents are a promising target to restore lost bladder control, as stimulation with different frequencies may be used to treat urinary incontinence and increase continent volumes or to generate stimulation-evoked bladder contractions for on-demand voiding. This work identified that co-stimulation of multiple afferent reflex pathways can enhance activation of spinal circuits and may enable improved bladder emptying in SCI when stimulation of a single pathway is not sufficient.


Assuntos
Terapia por Estimulação Elétrica , Traumatismos da Medula Espinal , Uretra/inervação , Bexiga Urinária/fisiopatologia , Incontinência Urinária/terapia , Urodinâmica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reflexo , Traumatismos da Medula Espinal/complicações , Incontinência Urinária/etiologia
20.
Am J Physiol Renal Physiol ; 313(3): F657-F665, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28615244

RESUMO

Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E2 (PGE2) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE2 vs. vehicle and PelN stimulation after intravesical PGE2 on cystometric parameters were quantified. Intravesical infusion of PGE2 resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE2 PelN stimulation reversed the PGE2-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.


Assuntos
Dinoprostona , Terapia por Estimulação Elétrica/métodos , Plexo Hipogástrico/fisiopatologia , Contração Muscular , Músculo Liso/inervação , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária/inervação , Urodinâmica , Animais , Modelos Animais de Doenças , Eletromiografia , Feminino , Pressão , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Fatores de Tempo , Uretra/inervação , Bexiga Urinária Hiperativa/induzido quimicamente , Bexiga Urinária Hiperativa/fisiopatologia
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