Urethral Stimulation Research Articles

Evidence of a functional effect of transient transurethral catheterization on micturition in women

The objective of this study is to evaluate the effect of transient catheterization on uroflow parameters. Consenting women (ages 18-90) provided an uninstrumented uroflow pre- and post-indicated in urodynamic procedures. Voided volume, Qmax, and Qave were recorded for both uninstrumented uroflows. Uroflow curves were classified as "normal" or "abnormal." Pre- and post-urodynamic uroflow data were compared. Thirty-five patients were included in the study. There was a statistically significant decrease in Qave from the pre- to the post-urodynamic uroflows from 14.71 to 10.55 ml/s (p = 0.012). Additionally, 28.6% of uroflow tracing patterns changed from "normal" to "abnormal," whereas only one (2.9%) changed from "abnormal" to "normal" (p = 0.031). This study showed a degradative effect of transient catheterization on uroflow parameters, suggesting that catheterization may cause more than simply a passive obstructive effect. Urethral stimulation due to catheterization may perturb detrusor urethral function, altering voiding and possibly filling performance.

Urethral Sensations are Related to the Development of Detrusor Overactivity.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

Participation of Endogenous Opioids in the Inhibition of the Spinal Generator for Ejaculation in Rats

A spinal pattern generator controls the expression of ejaculation. When this ejaculation generator is activated it can be phasically controlled, at a spinal level, by intrinsic mechanisms that eventually lead to the establishment of both short- and long-lasting inhibitory processes. To evaluate the hypothesis that endogenous opioids participate in the control of ejaculation by exerting an inhibitory influence upon the spinal generator for ejaculation. Electromyographic recordings of the ejaculatory motor pattern recorded in the bulbospongiosus muscles were obtained as physiological markers of ejaculation. By using a model for the study of ejaculation in spinal male rats, we analyze the effects of the intravenous injection of the opioid agonist morphine and the opioid antagonist naloxone on the expression of the ejaculatory motor pattern. In addition, the effect of pre-treatment with systemic naloxone on the establishment of the inhibition of the ejaculatory motor pattern resulting from its repeated sensory-induced elicitation was evaluated. Data obtained show that: (i) the i.v. injection of morphine (1-10 mg/rat) inhibits whereas that of naloxone (1-10 mg/rat) induces the expression of the genital ejaculatory motor pattern; (ii) naloxone pretreatment dose-dependently blocks the inhibitory effects of the high dose of morphine upon the rhythmic motor pattern of ejaculation; (iii) the inhibition of the ejaculatory response induced by repeated urethral stimulation can be delayed, and the ejaculatory capacity augmented, by naloxone injection (10 mg/rat). Together, these evidences support the notion that endogenous opioids modulate the activity of the spinal generator for ejaculation by exerting an inhibitory influence.

Increase of ejaculatory capacity by systemic administration of the oquichpatli ( Senecio cardiophyllus) aqueous crude extract in male rats

Aim of the study To analyse the pro-ejaculatory properties of the proverbial Mexican plant oquichpatli, Senecio cardiophyllus, in an animal model for the study of ejaculation in spinal and anaesthetised male rats. Materials and methods The aqueous crude extract of Senecio cardiophyllus (at 0.4, 1.2 and 4 mg/kg) was i.v. administered to (a) anaesthetised and spinalised male rats after spinal cord transection and (b) anaesthetised and spinalised male rats previous to the inhibition of ejaculation elicited by repeated urethral stimulation. The motor pattern of ejaculation and the development of its inhibition were analysed under the influence of the aqueous crude extract of Senecio cardiophyllus and compared to urethrally induced ejaculations. Results Systemic administration of the Senecio cardiophyllus aqueous crude extract, at all tested doses, induced the ejaculatory response in male rats. This response was featured by a statistically significant augmented number of ejaculatory discharges when compared to control animals. Oquichpatli-induced ejaculatory responses included the expression of autonomic and motor components of ejaculation and the potent expulsion of urethral contents and seminal plugs. Administration of oquichpatli aqueous crude extract prevented the inhibition of ejaculation elicited by urethral stimulation by promoting a statistically significant increase in the expression of ejaculatory motor patterns. Conclusion Present findings show by the first time that the aqueous crude extract of Senecio cardiophyllus possesses the ability to increase the ejaculatory capacity in male rats.

The Response of the Corporal Tissue and Cavernosus Muscles to Urethral Stimulation: An Effect of Penile Buffeting of the Vaginal Introitus

We investigated the hypothesis that urethral stimulation in humans induces sexual response in the form of activation of the corporal tissue and cavernosus muscles through a reflex mechanism. Electromyographic activity of corpora cavernosa (CC), corpus spongiosum (CS), bulbocavernosus (BCM), and ischiocavernosus (ICM) muscles was recorded in 43 healthy volunteers (24 men, 19 women; age, 37.7 +/- 8.2 years) during urethral stimulation. The tests were repeated after individual anesthetization of urethra, CC, CS, BCM, and ICM. During stimulation of the distal urethra, slow wave variables of CC and CS decreased while motor unit action potentials of BCM and ICM increased. Urethral stimulation after individual anesthetization of urethra, CC, CS, BCM, and ICM did not effect significant changes in these structures, but saline administration did. Diminished electromyographic activity of CC and CS with increased activity of BCM and ICM during distal urethral stimulation presumably denotes sinusoidal muscle relaxation of CC and CS and cavernosus muscles' contraction. Sinusoidal muscle relaxation and contraction of cavernosus muscles upon distal urethral stimulation are suggested to be mediated through a reflex that we call the "urethro-corporocavernosal reflex." Sinusoidal and cavernosus muscles' response during coitus appears to effect a degree of tumescence for both male and female partners.

Effect of Urethral Stimulation on Vesical Contractile Activity

We investigated the hypothesis that urethral stimulation effects vesical contraction. Vesical pressure response to urethral balloon distension with normal saline in increments of 1 mL was recorded in 26 healthy volunteers (17 men, 9 women; mean age, 36.9 +/- 9.7 SD years) before and after individual anesthetization of the urinary bladder and urethra. Urethral distension was effected by a 6F balloon-ended catheter introduced per urethra. Vesical pressure was measured by means of a microtip catheter. Vesical pressure recorded gradual increase on increase of urethral balloon distension. Bladder response was maintained as long as urethral distension was continuous. The response showed no significant difference when we distended different parts of the male or female urethrae. Urethral distension after individual vesical and urethral anesthetization effected no change in the vesical pressure. Urethral distension produced a vesical pressure increase that presumably denotes vesical contraction. Vesical contraction on urethral stimulation by distension is suggested to be mediated through a "urethrovesical stimulating reflex" that seems to facilitate vesical contraction. Provided further studies to be performed in this respect, the reflex may prove to be of diagnostic significance in micturition disorders.

The effect of external urethral sphincter contraction on the cavernosus muscles and its role in the sexual act

A study of the effect of external urethral sphincter contraction on ischio-/bulbo-cavernosus muscles could not be traced in the literature. We investigated the hypothesis that external urethral sphincter contraction induces cavernosus muscles' contraction. Twenty-one healthy volunteers (age 37.6 +/- 9.7 SD years, 12 men, nine women) were studied. The electromyographic response of the ischio- and bulbo-cavernosus muscles to external urethral sphincter stimulation was recorded before and after anesthetization of the external urethral sphincter, and the ischio- and bulbo-cavernosus muscles; the response was also recorded using normal saline instead of lidocaine. Upon external urethral sphincter stimulation (five square pulses, 1 ms duration, 53.8 +/- 10.2 mA threshold), both cavernosus muscles exhibited increased electromyographic activity with a mean amplitude of 386.2 +/- 44.9 microV for the ischio-cavernosus and 318.4 +/- 36.6 microV for the bulbo-cavernosus muscle. The mean latency read 16.8 +/- 1.3 ms for the ischio-cavernosus muscle and 15.7 +/- 1.2 ms for the bulbo-cavernosus muscle. Neither the ischio- nor the bulbo-cavernosus muscle responded to stimulation of the anesthetized external urethral sphincter, but both responded after saline administration. Likewise, the anesthetized ischio- and bulbo-cavernosus muscles showed no response to external urethral sphincter stimulation but responded after saline had been injected. Increased electromyographic activity of the two cavernosus muscles on external urethral sphincter stimulation presumably denotes contraction of these two muscles and that this action is probably reflex, mediated through the 'sphinctero-cavernosus-reflex'. Cavernosus muscles' contraction assists in the erectile and ejaculatory mechanisms. It is suggested that this reflex be included as an investigative tool in the diagnosis of erectile and ejaculatory disorders, provided further studies are performed.

Cholinergic modulation of the urethro genital reflex in spinal cord-transected rats

The aim of this study was to determine which of the muscarinic receptor subtypes are involved in the modulation of the urethrogenital reflex (UGR) in male, spinal cord-transected rats. The electromyographic (EMG) responses of the bulbospongiosus muscle (BS) to the topical spinal application of muscarine and the combination of muscarine and the selective muscarine receptor antagonists methoctramine (M2), AFDX (M2), 4DAMP (M3) and tropicamide (M4) were determined before and after the elicitation of UGR by way of the mechanical stimulation of the urethra. When 50- and 100-μg doses of muscarine were applied without urethral stimulation, a rhythmic activity of the BS was observed, similar to the one found when UGR was evoked. The M3 and M4 – but not the M2 – antagonists prevented BS response to muscarine when urethral stimulation was not performed. When UGR was elicited following urethral stimulation muscarine produced an increase in burst duration and a decrease in burst frequency. The M2 antagonist reverted the effects of muscarine on the UGR, while the M3 and M4 antagonists produced a significant increase in the frequency and in the bursts number, when compared to the control muscarine response. The differences observed in BS responses to muscarine and muscarine antagonists before and after UGR elicitation were probably linked to the intrinsic effects of the endogenous acethylcholine (Ach) released after urethral stimulation. The present results suggest a cholinergic modulation of UGR in spinal cord-transected rats mediated by the M2, M3 and M4 muscarinic receptor subtypes.

Effect of Micturition on the External Anal Sphincter: Identification of the Urethro-Anal Reflex

Background/Objective: A study on the response of the external anal sphincter (EAS) to the passage of urine through the urethra during micturition could not be found in the literature. We investigated the hypothesis that urine passage through the urethra effects EAS contraction to guard against possible flatus or stool leakage during micturition.Methods: The study was performed in 23 healthy volunteers (age, 38.6 ± 10.8 [SD] years; 14 men and 9 women). The EAS electromyogram (EMG) was performed during micturition by surface electrodes applied to the EAS. Also, the EAS EMG response to urethral stimulation by a catheter-mounted electrode was registered. The test was repeated after individual anesthetization of the EAS and urethra.Results: The EAS EMG recorded a significant increase (P < 0.01) during micturition and on urethral stimulation at the bladder neck. Stimulation of the prostatic, membranous, or penile urethra produced no significant change in the EAS EMG. Urethral stimulation after individual EAS and urethral anesthetization did not cause any changes in the EAS EMG.Conclusions: Urine passing through the urethra or urethral stimulation at the vesical neck produced an increase in the EAS EMG, which presumably denotes EAS contraction, which seems to guard against flatus or fecal leakage during micturition. EAS contraction on urethral stimulation is suggested to be mediated through a urethra-anal reflex. Further studies on this issue may potentially prove the diagnostic significance of this reflex in micturition and defecation disorders.

Exhaustion of the coital reflex in spinal male rats is reversed by the serotonergic agonist 8-OH-DPAT

Previous studies from our laboratory have shown that the genital motor pattern associated to the coital reflex in spinal male rats becomes exhausted when repeatedly evoked. Exhaustion of the genital motor pattern could be related to the sexual exhaustion phenomenon observed in copulating male rats. The present study was aimed to describe the features of coital reflex exhaustion and to determine if the 5-HT 1A agonist 8-OH-DPAT was able to reverse exhaustion of this ejaculatory-like response. Additionally, the effect of pre-treatment with the 5-HT 1A antagonist WAY 100635 on the 8-OH-DPAT induced motor response was evaluated. Results revealed that development of coital reflex exhaustion initiated with a progressive increase in the latency of response and was characterised by a change in the properties of the motor pattern itself. Once exhausted, i.v. administration of 8-OH-DPAT provoked the immediate expression of a potent motor pattern similar to the coital reflex, but in the absence of urethral stimulation. Injection of WAY 100635 induced, per se, expression of the coital reflex after exhaustion. Notwithstanding, pre-treatment with WAY 100635 was able to block the 8-OH-DPAT-induced motor response implying that its effect was exerted upon 5-HT 1A receptors. Data suggest that the sexual exhaustion phenomenon might possess a spinal component.

The urethrodetrusor facilitative reflex in women: Results of urethral perfusion studies

Objective: This study was undertaken to describe the effects of urethral perfusion on bladder activity, urethral pressure, and sensation in patients with either incontinence or prolapse or both of these. Study Design: Among 76 consecutive patients who were seen for urodynamic evaluations, 63 had vesical, abdominal, and urethral pressures measured while the urethra was perfused with fluid. A perfusion study result was considered positive if the perfusion provoked a detrusor contraction. Results: Of the 63 women 9 (14%) had a positive urethral perfusion study result, and all of them had detrusor instability independent of perfusion. Among the women with detrusor instability 53% (n = 9/17) had positive study results, versus none of the 46 women without detrusor instability ( P = .000001). Women with mixed incontinence were more likely to have a positive perfusion test result (n = 4/7; 57%) than were those without mixed incontinence (n = 5/56; 10%; P = .006), although urethral hypermobility was not significantly associated with a positive test result. Among the subjects 60% experienced urgency during perfusion, and in half of these urethral pressure was concurrently increased. Among those who had no urgency 84% demonstrated decreased urethral pressure ( P = .01). Conclusions: Positive perfusion study results were more common among women with detrusor instability but did not discriminate any patient with detrusor instability whose condition was not diagnosed by standard urodynamic studies. The association of positive perfusion study results with mixed incontinence seems primarily related to poor central inhibition of detrusor activity rather than to urethral stimulation. (Am J Obstet Gynecol 2000;182:794-804.)

SYNAPTIC RESPONSES EVOKED BY LOWER URINARY TRACT STIMULATION IN SUPERIOR CERVICAL GANGLION CELLS IN THE RAT

Stimulation of afferent neurons from the urinary tract can evoke powerful cardiovascular reflexes in animals and in humans. Here we tested whether and to what extent postganglionic sympathetic neurons projecting to the head and neck are involved in these reflexes. In adult anesthetized female Wistar rats, reflex changes in synaptic activity elicited from the lower urinary tract were recorded in neurons of the superior cervical ganglion using intracellular recording techniques. Gentle movements of the urethral cannula and/or slow injections of 0.3 to 0.6 ml. saline into the bladder modified synaptic activity in 75% of neurons tested: 11/15 neurons tested showed reflexes to urethral stimulation (8 excitatory, 3 inhibitory) and 8/12 neurons responded to bladder distension (5 excitatory, 3 inhibitory). Five neurons showed a reciprocal response pattern to the two stimuli. Suprathreshold and subthreshold inputs to a given cell mostly showed the same type of response. There was no evidence that urinary tract stimulation recruited preganglionic inputs that did not have ongoing activity prior to the stimulus. Reflexes from the lower urinary tract clearly reached sympathetic neurons located in remote segments. The response incidence in the population studied suggests that most sympathetic neurons involved in cardiovascular regulation participate in these reflexes. The different reflex patterns probably occur in neurons with different functional targets in the head and neck.

Evaluation of clinical indexes to predict fate of pelvic nerve dysfunction.

This study was designed to evaluate posterior urethral sensation and sacral reflex evoked by posterior urethral stimulation to predict fate of pelvic nerve dysfunction. Enrolled were 24 male patients sequentially receiving the following examinations 1-3 months (postoperative) and more then 6 months (follow-up) after surgery for rectal cancer: sensory thresholds of the penile skin (SS) and the posterior urethra (SU), sacral reflex evoked by penile stimulation (BCR) and posterior urethral stimulation (UUR), and urodynamic study. Controls included 25 patients with normal voiding function before pelvic surgery. SS, SU and latencies of BCR and UUR averaged 1.9+/-0.6 mA, 5.6+/-1.8 mA, 33.3+/-4.2 ms and 65.0+/-9.3 ms in controls, respectively, and unchanged postoperatively in 13 patients with normal voiding function. Of 11 patients with voiding dysfunction whose SS and latency of BCR remained unchanged, SU increased in 7, voiding function remained unrecovered in 6 patients during the follow-up period and recovered in the remaining 5. None of four patients with nonevocable UUR recovered voiding function. Thus, unchanged SU and disappearance of UUR were useful to predict recovery and nonrecovery of postoperative voiding dysfunction, respectively.

PERIPHERAL DISTRIBUTION OF THE HUMAN DORSAL NERVE OF THE PENIS

Purpose The integrity of the dorsal nerve of the penis is crucial for normal erectile and ejaculatory function. To our knowledge a description of this nerve along the phallus has not been formally described. We illustrate the distribution of the dorsal nerve of the penis to the penile shaft, anterior urethra and glans. Materials and Methods Neuroanatomical dissections were performed on 28 cadaver penis specimens. Electrodiagnostic testing was conducted on 10 healthy male subjects to confirm the anatomical findings. Results The dorsal nerve of the penis consists of 2 populations of axons, one to innervate the penile shaft and urethra, and the other to innervate the glans. Stimulation of the urethra resulted in responses recorded in the main trunk of the dorsal nerve of the penis and stimulation of the nerve evoked responses within the urethra. Bulbocavernosus muscle contraction was elicited following urethral stimulation. Conclusions Urethral innervation by the dorsal nerve of the penis supports the view that urethral afferent impulses are a component of reflex ejaculatory activity. The pattern of glanular innervation by the dorsal nerve of the penis identifies the glans as a sensory end organ for sexual reflexes. The undulating character of the dorsal nerve of the penis is a mechanism by which the nerve can accommodate to significant changes in penile length with erection. Electrodiagnostic studies of the dorsal nerve of the penis should be modified to consider the anatomical findings.

Innervation of the human anterior urethra by the dorsal nerve of the penis.

Previous neuroanatomic studies have demonstrated that branches of the dorsal nerve of the penis (DNP) innervate the anterior urethra. This study utilized electrodiagnostic techniques to confirm this finding. Electrical stimulation of the urethra resulted in responses recorded in the main trunk of the DNP, and responses were recorded from the urethra following stimulation of the DNP. A bulbocavernosus reflex was evoked after urethral stimulation. Urethral afferent impulses have a role in reflex ejaculatory function.

Effects of Prenatal Morphine and Cocaine Exposure on Spinal Sexual Reflexes in Male and Female Rats

Vathy, I. and L. Marson. Effects of prenatal morphine and cocaine exposure on spinal sexual reflexes in male and female rats. PHYSIOL BEHAV 63(3) 445–450, 1998.—Previous studies demonstrated that in utero exposure to morphine or cocaine differentially alters adult sexual behaviors, which are dependent on circulating gonadal hormones in male and female rats. In the present study, the effects of in utero morphine and cocaine exposure on the urethrogenital reflex were examined. The urethrogenital reflex is thought to be a hormone-independent spinal sexual reflex in both males and females. This reflex is tonically inhibited by supraspinal neurons but can be consistently evoked by urethral stimulation in the spinally transected animals. Prenatal morphine or cocaine exposure did not remove the supraspinal inhibition of the urethrogenital reflex in spinally intact male or female rats. In spinally transected animals, the urethrogenital reflex was qualitatively similar in all groups. However, morphine-exposed males required a stronger stimulus to elicit the urethrogenital reflex but once elicited, the frequency of the urethrogenital reflex was significantly higher compared to either controls or cocaine-exposed males. In contrast, in female rats, neither prenatal morphine nor cocaine exposure had any effect on the urethrogenital reflex. Thus, the urethrogenital reflex appears to be differentially affected by prenatal exposure to morphine in males and females.

A role for 5-hydroxytryptamine in descending inhibition of spinal sexual reflexes.

Neurons in the region of the rostral nucleus paragigantocellularis (nPGi) mediate the inhibition of spinal sexual reflexes. Anatomical and pharmacological evidence is presented supporting a role for 5-hydroxytryptamine (5-HT) in this inhibition. Neurons in the rostral nPGi project to the ventral horn in the vicinity of the pudendal motoneurons. A significant number (78% ipsilateral) of these neurons contain 5-HT. Anterograde tracing with Phaseolus leucoagglutinin (PHA-L) confirmed the nPGi projection to pudendal motoneuron and interneuronal areas of the lumbar cord. 5-HT immunoreactive fibers and presumptive terminals surround the pudendal motoneurons. Urethral stimulation, in the anesthetized male rat, elicited penile erections, ejaculation and rhythmic contractions of the perineal muscles, we have used the term coitus reflex to describe this response. Intrathecal injection of 5-HT (4-50 micrograms) abolished the coitus reflex. Methysergide (1-10 mg/kg i.v.) prevented the 5-HT induced blockade of the coitus reflex. These data support the hypothesis that 5-HT is involved in the descending inhibition of spinal sexual reflexes.

Restoration of voiding function

A review is given on the major newer techniques employed in bladder function restoration and rehabilitation. A special emphasis is made on the major contributions of intermittent clean self-catheterization, the artificial urinary sphincter, the use of detubularized bowel, urethral and prostatic stents and anterior sacral nerve root stimulation with and without posterior sacral rhizotomy. The necessity of an organized team work is stressed.

A model for the study of sexual function in anesthetized male and female rats

A preparation for the study of sexual function in anesthetized spinal male and female rats is discussed. Urethral stimulation in males elicited penile erection, ejaculation, and rhythmic contractions of the striated perineal muscles. In females, vaginal and uterine contractions and rhythmic contractions of the perineal muscles were elicited. These responses show many similarities to responses seen during sexual climax in unanesthetized humans and animals. This response, which we refer to as the urethrogenital reflex, is unaffected in either sex by gonadectomy. We determined that the urethrogenital reflex is produced by a spinal pattern generator and is under tonic descending inhibition from the brain stem. We conclude that this preparation may be a valuable model for experimental study of the neural mechanisms of sexual function in both sexes.

The ejaculatory reflex in copulating rats: normal bulbospongiosus activity without apparent urethral stimulation

Electromyographic activity was recorded from the bulbospongiosus muscles of intact, copulating male rats to test the hypothesis that urethral stimulation contributes to the ejaculatory reflex. Neither urethral anesthetization with lidocaine nor prevention of emission with guanethidine affected the rhythmic contraction of the bulbospongiosus muscle during the ejaculatory pattern. Urethral stimulation by the ejaculate apparently does not contribute to the regulation of the striated-muscle components of ejaculation-related reflexes in copulating male rats.