Urodynamic action of clonidine in the chronic spinal cat

Spinalization produces a central micturition dysreflexia characterized by weak vesical contraction reflexes and by an exaggerated urethro-urethral contraction reflex, causing the peripheral syndromes of underactive detrusor and detrusor-sphincter dys-synergia. We explored the action of catecholaminergic drugs of central action on these micturitional dysfunctions. Twenty-four male cats were spinalized by transection of the spinal cord at C5–C6 level and studied 1–18 weeks later. Cystosphincterograms were performed without using anesthetic drugs. Pves, Pura, the EMG of the external sphincter, the EMG of the extensor hindleg muscles, and urine emission were studied. The responses of the spinal vesicovesical contraction, urethro-vesical contraction, and urethro-urethral contraction reflexes were explored. Clonidine (0.02–0.06 mg/kg intravenously [IV], intraperitoneally [IP], or per os), phentolamine (0.7–1 mg/kg, IV), and yohimbine (0.4–1 mg/kg, IV) were administered. Clonidine, at doses of 0.02 mg/kg, IV or IP, or higher, produced the following effects: (1) it significantly increased the intensity and duration of Pves waves; (2) it inhibited the spasms of the external sphincter; (3) it induced voiding; (4) it reduced spasticity; (5) it reinforced the vesico-vesical contraction reflex; (6) it antagonized the exaggeration of the urethro-urethral contraction reflex; (7) it corrected totally or partially the underactive detrusor and detrusor-sphincter dys-synergia. Taken orally (0.02–0.03 mg/kg) the urodynamic effect of clonidine was not significant; higher doses produced vomiting and other adverse effects. The action of clonidine was blocked by yohimbine but not by phentolamine. These results suggest that the absence of the descending noradrenergic pathways plays a role in the physiopathology of neurogenic bladder dysfunctions in chronic spinalized cats.     

Residual urine,underactive detrusor function,and the nature of detrusor/sphincter dyssynergia

In a group of 280 patients with mixed pathology the adequacy of the detrusor contraction during voiding has been assessed by a new method. For the group as a whole, residual urine is nearly always the result of the fading away of the detrusor contraction and rarely of premature sphincter contraction. It is strongly associated with failure to attain an adequate detrusor contraction at any time during the micturition. The same is true both for children who show consistent urethral overactivity during voiding and for patients with detrusor/sphincter dyssynergia of neuropathic origin. The results suggest that in detrusor/sphincter dyssynergia or other types of urethral overactivity, it may be misleading to ascribe inefficient bladder emptying solely to the obstructive effect of the urethral closure mechanism; the underactive detrusor function should also be taken into account. Often there appears to be an incomplete activation of the micturition reflex, resulting in both incomplete stimulation of the detrusor and incomplete relaxation of the urethral closure mechanism.     

Effect of naloxone on detrusor-sphincter dyssynergia in the chronic spinal cat

Naloxone, an opioid peptide antagonist, has been reported to facilitate voiding in neurologic bladder disorders, but its effects on the neural micturition reflex arc are poorly understood. We studied the effect of naloxone in 34 male adult cats, spinalized at C5-C6 level 7 to 119 days previously. Each cat served as its own control. The following tests were performed: Urethral pressure profiles, cystosphincterograms with the urethro-vesical junction opened and closed and mechanograms of the detrusor, and the circular and longitudinal urethral muscles. The study included (1) the effects of anesthesia of the bladder and pelvic nerve, as well as that of the urethral and pudendal nerves; (2) the action of naloxone; and (3) the action of oxymorphone. Our results demonstrated that naloxone (1) increased somatic (osteotendinous and nociceptive) reflexes and aggravated spasticity; (2) increased vegetative micturitional and sexual reflexes, in particular the urethra-urethral contraction reflex, aggravating the spasmodic contractions of the external sphincter; and (3) increased the frequency and intensity of the mass reflex. In consequence, we suggest that naloxone is contraindicated in cases of spinal cord lesions with detrusor-sphincter dyssynergia syndrome.     

A study of the continence mechanism of the external urethral sphincter with identification of the voluntary urinary inhibition reflex

PURPOSE: The role of the external urethral sphincter in the opposition and interruption of the act of voiding was investigated. MATERIALS AND METHODS: The study included 7 men and 5 women with a mean age plus or minus standard deviation of 38.6 +/- 11.2 years. The bladder was filled with saline up to the urge sensation. Detrusor and posterior urethral pressures were recorded before and upon resisting the reflex detrusor contraction, and upon interrupting voiding by voluntary external urethral sphincter contraction. The test was repeated by interrupting the urinary stream with external urethral sphincter electrostimulation. The electromyography response of the internal urethral sphincter to the suppression and interruption of voiding was documented before and after internal urethral sphincter anesthetization. RESULTS: Suppression of the reflex detrusor contraction as well as of urinary stream interruption by external urethral sphincter contraction voluntarily or by electrostimulation resulted in a significant detrusor pressure decrease (p <0.01) and urethral pressure increase (p <0.001). Internal urethral sphincter electromyography activity, which normally disappears during voiding, was still present. After internalurethral sphincter anesthetization subjects suppressed the reflex detrusor contraction by voluntary external urethral sphincter contraction for a mean of 62.6 +/- 9.6 seconds, after which involuntary voiding occurred. The internal urethral sphincter showed no electromyography activity. CONCLUSIONS: The external urethral sphincter induces continence by preventing internal urethral sphincter relaxation at the detrusor contraction, which is suggested to be reflex in nature and is called the voluntary urinary inhibition reflex, and by mechanically compressing the urethra. Contraction of the external urethral sphincter, which is a striated muscle, mechanically occludes the urethra for a few seconds, by which time the detrusor has relaxed as an effect of the voluntary inhibition reflex.     

Overactive bladder inhibition in response to pelvic floor muscle exercises

A recent study by the senior author demonstrated that striated urethral sphincter contraction effected the inhibition of vesical contraction and suppression of the desire to micturate, an action suggested to be mediated through the "voluntary urinary inhibition reflex". We hypothesized that the effect of pelvic floor muscle (PFM) exercises on the overactive bladder was mediated through this reflex action. The current communication investigates this hypothesis. A total of 28 patients (mean age 44.8+/-10.2 years, 18 men, 10 women) with overactive bladder and 17 healthy volunteers (mean age 42.6+/-9.8 years, 12 men, 5 women) were enrolled in the study. The vesical and posterior urethral pressures were determined before and after vesical filling reached the volume at which urge in control subjects, and involuntary voiding in the patients, occurred. Intra-abdominal pressure was recorded to obtain detrusor pressure readings. The bladder was refilled to the above volume and the subject asked to hold PFM contractions for 10 s during which the vesical and posterior urethral pressures were recorded. In healthy volunteers, the mean detrusor and posterior urethral pressures at urge to void were 30.6+/-4.8 SD and 18.7+/-3.3 cm H(2)O, respectively. On PFM contraction, the detrusor pressure declined to 11.6+/-1.4 cm H(2)O (P<0.01) and urethral pressure increased to 139.8+/-17.4 cm H(2)O (P<0.001). In patients, the mean detrusor and posterior urethral pressure readings when the bladder was filled to the volume which induced involuntary incontinence, were 28.2+/-4.2 and 17.3+/-3.4 cm H(2)O, respectively; on PFM contractions, the detrusor pressure decreased to 10.6+/-2.1 cm H(2)O (P<0.01), while urethral pressure increased to 86.6+/-7.9 cm H(2)O (P<0.001) and voiding did not occur. In conclusion, PFM contractions led to a decline of detrusor and increase of urethral pressures and suppressed the micturition reflex. These contractions appear to induce their effect by preventing internal sphincter relaxation produced by the micturition reflex. Failure of the internal sphincter to relax seems to cause reflex detrusor relaxation, an action presumably mediated through the "voluntary urinary inhibition reflex". The results of the current study encourage the treatment of overactive bladder with PFM contractions.     

Transurethral electroresection of the external urethral sphincter in the urological management of male tetraplegics

Transurethral electroresection of external urethral sphincter (TUR-sph) was performed in sixteen male tetraplegics to obtain good voiding efficiency and to prevent autonomic dysreflexia due to detrusor sphincter dyssynergia. Ratio of residual urine as a parameter of voiding efficiency and blood pressure and plasma noradrenaline level during voiding as parameters of the significance of autonomic dysreflexia were evaluated before and after TUR-sph, and all these parameters had significantly improved after TUR-sph. After discharge from the hospital, all patients urinated comfortably with the maneuver of suprapubic percussion by themselves and/or their helpmates, and no patients complained of any inconvenience due to urinary incontinence. Moreover, no patients had the episode of autonomic dysreflexia in daily life except for one patient who had it once with urinary tract infection. TUR-sph brings not only the improvement of voiding efficiency but also the effect as a safety valve against autonomic dysreflexia by means of preventing the occurrence of autonomic dysreflexia due to detrusor sphincter dyssynergia.     

Role of positive urethrovesical feedback in vesical evacuation. The concept of a second micturition reflex: the urethrovesical reflex

Upon feeling the urge to urinate, the urinary bladder contracts, the urethral sphincters relax and urine flows through the urethra. These actions are mediated by the micturition reflex. We investigated the hypothesis that vesical contraction is maintained by positive feedback through continuous flow of urine through the urethra, and that the cessation of urine flow aborts detrusor contraction. Normal saline was infused into the urinary bladders of 17 healthy volunteers (age 35.2 years±4.2(SD); ten women and seven men) at a rate of 100 ml/min. On urge, which occurred at a mean volume of 408.6 ml±28.7of saline, the subject micturated while the vesical and urethral pressures during voiding were being recorded; residual urine was measured. The test was repeated after anesthetizing the urethra with xylocaine gel or, on another occasion, after applying a bland gel . On micturition, the urine was evacuated as a continuous stream without straining; no residual fluid was collected. After urethral anesthetization, the fluid came out of the urethra in multiple intermittent spurts and only with excessive straining. There was a large amount of residual fluid (184.6 ml±28.4). The results of bland gel application showed no significant difference (P>0.05) from those without gel. Detrusor contraction during micturition is suggested to be maintained by positive urethrovesical feedback elicited by the continued passage of urine through the urethra. This feedback seems to be effected through the urethrovesical reflex, which produces vesical contraction on stimulation of the urethral stretch receptors. Abortion of this reflex by urethral anesthetization resulted in failure of detrusor contraction and excessive straining was needed to achieve bladder evacuation in multiple spurts. The urethrovesical reflex is thus assumed to constitute a second micturition reflex responsible for the continuation of detrusor contraction and urination. The role of this reflex in the pathogenesis of micturition disorders needs to be studied.     

External sphincter dyssynergia: an abnormal continence reflex

Some of the characteristics of detrusor-external sphincter dyssynergia were examined in 14 patients with traumatic upper motor neuron lesions within 44 weeks of injury. The sacral evoked response latencies of the male patients were shortened at any time after injury. A continence reflex could be demonstrated in most patients at any time after injury. Comparing averaged values for the group at 4-week intervals, resting pressure at the external urethral sphincter and post-void residual volumes reached nadirs at 12 weeks while voiding efficiency peaked at this time. Thus, voiding function appears to be optimal 12 weeks after injury. During reflex detrusor activity, increases in external urethral sphincter electromyographic activity and external urethral sphincter pressure were associated clearly with a positive slope of the intravesical pressure trace, whereas decreases in both parameters were associated with a negative slope. Voiding occurred only during a negative slope. Although propantheline induced detrusor areflexia, episodic peaks in external urethral sphincter pressure and electromyographic activity continued to occur. We propose that external sphincter dyssynergia, which is independent of detrusor contraction, is the continence reflex exaggerated owing to the loss of supraspinal influences. We believe that the multiple patterns of dyssynergia described previously by others are variations, largely owing to technique, of the single pattern we have observed. The observation of synergic-like urethral responses in some patients during a negative slope of the intravesical pressure, even with complete suprasacral spinal lesions, implies existence of a pathway for synergic-like voiding in the spinal cord.     

Experimental and clinical studies of urethral anesthesia on etiology and treatment of detrusor-sphincter dyssynergia

We studied whether detrusor-sphincter synergia during micturition was obtained by means of urethral anesthesia with lidocaine hydrochloride in five thoracic spinal cats and eight clinical cases with detrusor-sphincter dyssynergia. In thoracic spinal cats with detrusor-sphincter dyssynergia, urethral anesthesia produced detrusor-sphincter synergia, an increase in the maximum bladder pressure and a decrease in the residual volume. In clinical cases with detrusor-sphincter dyssynergia, urethral anesthesia produced detrusor-sphincter synergia or a decrease in the external urethral sphincter activities during micturition, and a decrease in the maximum urethral closure pressure and the residual volume. There were no remarkable changes of the external urethral sphincter activities during urine storage phase before and after urethral anesthesia in both spinal cats and clinical cases. These results suggest that urethral anesthesia blocks the urethro-urethral contraction reflex and secondarily activates vesico-urethral relaxation reflex. The block of urethral sensory nerves is thought to effectively treat detrusor-sphincter dyssynergia.     

Control and coordination of bladder and urethral function in the brainstem of the cat

Stimulation and lesion experiments in the pontine tegmentum of 34 cats, with urodynamic measurements both pre- and peroperatively and during up to 4 months of follow-up, have confirmed the existence of two different brainstem regions concerned with lower urinary tract function. In the dorsolateral pontine tegmentum, a compact, dorsomediolaterally located M region, corresponding to Barrington's micturition centre, reacts specifically to electrical stimulation, causing prompt relaxation of the anal and urethral striated sphincters followed after about 2 s by detrusor contraction, as in normal micturition. Bilateral lesions in this M region lead to a 2–9 week period of urinary retention, during which detrusor activity is depressed and the bladder capacity increases. Stimulation in a larger, more diffuse, more laterally located L region elicits sphincter activity: contraction of the striated urethral sphincter together with an increase in the anal-sphincter EMG, or relaxation of the striated urethral sphincter together with either a decrease or an increase in the anal-sphincter EMG. Provided lethal respiratory complications can be avoided, bilateral lesions in this L region lead after a few days to a state, lasting up to 2 months, in which there is urinary incontinence accompanied by a decrease in the bladder capacity and detrusor overactivity. Neither type of lesion leads to true detrusor-urethra dyssynergia. However, because the amplitude of anal-sphincter EMG sometimes increases when the striated urethral sphincter relaxes, observations of the anal-sphincter EMG can misleadingly suggest dyssynergia. Brainstem mapping of the results of stimulation suggests a motor pathway running from the M to the L region and another descending caudally from the L region. The observations suggest that the M region forms a true micturition centre, facilitating the detrusor voiding contraction and also (via the presumptive connection with the L region) ensuring synergic sphincter relaxation. The L region appears not only to relay this voiding sphincter relaxation, but to be responsible for control of the pelvic floor and its sphincters in general, and for helping to maintain urinary continence.     

Refractoriness of urethral striated sphincter during voiding: studies with afferent pudendal reflex arc stimulation in male subjects

To assess the excitability of the striated sphincter under normal and abnormal conditions, electrostimulation of the periurethral striated sphincter via the dorsal nerve of the penis was done with the patient at rest and during voiding. Monitoring of simultaneous intravesical and intramembranous urethral pressures, and electromyographic responses of the striated sphincter was performed under fluoroscopic guidance in 14 male subjects. The urethral striated sphincter attained a state of relative refractoriness during detrusor contraction (voiding phase) and greater amounts of afferent stimulation were required to elicit sphincter contractile activity compared to the amounts required during resting states. Under conditions of a hyperactive detrusor with synergic voiding, the amounts of stimulation required to elicit striated sphincter responses were higher than those required in normal subjects. On the other hand, under conditions of striated sphincter dyssynergia, minute amounts of afferent stimulation were enough to produce sphincter contraction during voiding.     

The after-contraction: a true detrusor contraction or a late dyssynergic urethral sphincter contraction?

OBJECTIVE: To evaluate the mechanism and significance of the after-contraction, recorded in bladder pressure by urodynamics, at the end of micturition. PATIENTS AND METHODS: The urodynamic recordings showing an after-contraction of the detrusor in 65 patients of all ages and with a variety of pathologies were re-examined. Special attention was directed to the anal or urethral sphincter needle electromyographic activity and to the monitored urethral pressure, to determine any relationships with the patterns of detrusor pressure. RESULTS: An after-contraction was noted in 61 patients with detrusor instability and in 11 with urethral instability. In 59 patients it was evident that the after-contraction, i.e. a renewed increase in detrusor pressure during the declining contraction, correlated with a sphincter contraction preceding it by a fraction of a second. Similar increases in detrusor pressure were apparent in patients with detrusor-sphincter dyssynergia throughout voiding. In six patients the relationship was less clear mainly because there were artefacts in the curves. CONCLUSION: The after-contraction arises by a sudden stopping of the outflow of urine, provoked by a sphincter contraction. This may occur by involuntary dyssynergia or by an early voluntary interruption of the voiding stream. The 'milk back' of urine from the proximal urethra to the bladder and the inhibited detrusor contraction (if the perineal contraction is prolonged) may cause some postvoid residual urine. It occurs mainly in the presence of detrusor and/or urethral instability.     

Urodynamic biofeedback: a new approach to treat vesical sphincter dyssynergia.

Some children with vesical sphincter dyssynergia are refractory to conventional pharmacologic therapy. Three such patients were treated using a method of sphincter retraining, biofeedback. They observed the urinary sphincter electromyogram while voiding to appreciate visually the abnormality. Two children learned to suppress voluntarily the inappropriate sphincter contraction during voiding. This normalized the subsequent electromyographic recordings and offered subjective improvement in the voiding symptoms. Retraining the urethral sphincter dysfunction may be approached using biofeedback techniques in selected patients.     

Effect of urethral dilation on vesical motor activity: identification of the urethrovesical reflex and its role in voiding

PURPOSE: We investigated the hypothesis that mild urethral distention, which presumably occurs during the passage of urine through the urethra, stimulates stretch receptors in the urethral wall, leading reflexively to vesical contraction. MATERIALS AND METHODS: We evaluated 9 male and 10 female healthy volunteers with a mean age +/- SD of 39.6 +/- 8.3 years. The posterior urethra was distended by a balloon filled with saline in 1 ml. increments up to 6 ml., while recording vesical pressure. The test was repeated after individual anesthetization of the urethra and bladder. RESULTS: Vesical pressure increased significantly at 1 and 2 ml. urethral distention (p <0.01). Increases in urethral distention effected further vesical pressure elevation (p <0.001), although there was no significant difference in distention at 3 to 6 ml. (p >0.05). No significant vesical pressure response of the individually anesthetized urethra or bladder occurred during urethral distention. CONCLUSIONS: Urethral distention is thought to cause vesical contraction through the stimulation of urethral stretch receptors. Vesical contraction at urethral distention postulates a reflex relationship that was abolished by individual anesthetization of the urethra and bladder. This relationship, which we call the urethrovesical reflex, appears to have a role in maintaining vesical contraction during voiding. Further studies are required to investigate the role of this reflex in voiding disorders.     

排尿期尿道测压的临床应用

目的：确定下尿路梗阻及其梗阻部位。方法：对４１例有下尿路梗阻症状患者进行了排尿期尿道测压（ＭＵＰＰ）,其中包括前列腺增生症（ＢＰＨ）２９例,男性尿道狭窄３例,逼尿肌－外括约肌协同失调３例,女性压力性尿失禁４例,女性尿道末端缩窄综合征１例,前例腺炎１例。结果：２９例ＢＰＨ患者中,２６例有梗阻,其中梗阻位于膀胱颈部２０例;３例逼尿肌－外括约肌协同失调患者表现为外括约肌部压力下降;４例女性压力性尿失禁患     

Botulinum toxin as a new therapy option for voiding disorders: current state of the art

Botulinum toxin is a presynaptic neuromuscular blocking agent inducing selective and reversible muscle weakness up to several months when injected intramuscularly in minute quantities. Different medical disciplines have discovered the toxin to treat mainly muscular hypercontraction. In urology, indications for botulinum-A toxin have been neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, motor and sensory urge and, more recently, chronic prostatic pain. The available literature was reviewed using Medline Services. The keywords "botulinum-A toxin", "detrusor-sphincter dyssynergia", "neurogenic bladder", "spinal cord injury", "denervation", "chronic prostatic pain", "chronic urinary retention" were used to obtain references. A toxin injection is effective to treat detrusor-sphincter dyssynergia when injected either transurethrally or transperineally. After treatment, external urethral sphincter pressure, voiding pressure and post-void residual volume decreased. The effect lasts between 2 to 9 months depending on the number of injections. Best indications seem to be multiple sclerosis and incomplete spinal cord injury patients suffering from neurogenic detrusor overactivity and detrusor-sphincter dyssynergia. According to the previous results, the use of botulinum-A toxin injections into the external urethral sphincter has been extended to a variety of bladder obstructions and to decrease outlet resistance in patients with acontractile detrusor. In cases of successful treatment, spontaneous voiding re-occurs and catheterization can be resumed. Injections of the toxin into the external urethral sphincter also seem to have a beneficial effect on chronic prostatic pain, presumably by reducing hypertonicity and hyperactivity of the external urethral sphincter. Injections of botulinum-A toxin into the detrusor muscle has first been tested to treat neurogenic detrusor activity in spinal cord injured patients and in myelomeningocele children. Long lasting (mean 9 months) detrusor relaxation occurs after injection of usually 300 units of Botox). Continence is restored in about 95% of the patients and anticholinergic drugs can be markedly reduced or even stopped. Excellent results of botulinum-A toxin injections into the detrusor in neurogenic detrusor overactivity have lead to an expansion of this treatment to incontinence due to idiopathic detrusor overactivity. Although preliminary results are promising, adequate dosage of the toxin required for this indication is not yet known. In conclusion, it appears that botulinum toxin injection into either the external urethral sphincter or the detrusor offers new promising treatment options for many different urological dysfunctions. However, large controlled trials are absolutely required to establish the role of botulinum-A toxin injections in the fields of urology and neurourology on evidence based medicine.     

Computer simulation of the neural control of bladder and urethra

A large number of neural reflex loops may be involved in voiding and leak-free storage of urine. The simplifying hypothesis that only very few reflexes are needed to account for most of the observed behavior has been tested by quantitative simulation of the lower urinary tract and its control system. The mechanical part of the simulation, involving detrusor contraction strength and a carefully defined urethral resistance, is based on previous work. The postulated neural control system involves two mutually inhibitory control regions, leading to a bistable (storage-voiding) system, and reflexes driven by a single afferent signal with contributions from bladder wall tension and urethral distension. Because the control system is bistable, each of the two afferent contributions has two possible effects, so that four distinct reflexes appear to operate. Simulations, with and without these reflexes, show that this system accounts for many features of normal voiding, stop tests, and catheter voiding. The behavior is not sensitive to arithmetic details of the calculations involved. After triggering by a simulated suprapontine control signal, the voiding detrusor contraction is initially amplified by the afferent signal from the detrusor but it is sustained until the bladder is empty by the urethral afferent. Mechanical urethral obstruction causes slight residual urine. Breakdown of the mutual inhibition of the two control regions leads to detrusor instability, suggesting that this condition may sometimes have a central origin.     

An electromyographic study of detrusor sphincter dyssynergia in the neurogenic vesical dysfunction. Part 1. Its type and further sub-typing based on the analysis of motor units

Simultaneous recordings of electromyography of the external urethral sphincter (EUS) and bladder pressure were performed in 73 patients. The majority (69 cases) were afflicted with neurogenic vesical dysfunction, while four with benign prostatic hypertrophy (BPH) were also examined as control. Detrusor sphincter dyssynergia (DSD), whereby EUS failed to relax on voiding attempt, was noted in 64 patients. By examining the patterns of DSD throughout the voiding, it was possible to classify them into three distinct types as done by Blaivas. Type 1 was found in 7 patients, Type 2 in 10 patients, and Type 3 in 47 patients. Synergic urethral sphincter activity (Type 0) was found in other 9 patients including all four with BPH. Voiding dysfunction as evaluable by residual urine rate tended to increase as the type deteriorated from 1 to 3. Analysis of motor units revealed that the units noted during continent phase of the bladder disappeared (A0), decreased (A1), and retained or rather increased their activity (A2) during voiding attempt with (B1) or without (B0) recruitment of new units. A0B1 was found in 3 patients, A1B1 in 7, A2B1 in 32, A2B0 in 4, and A1B0 in 2. Again there was a tendency for voiding function to deteriorate as motor units sub-type changed from A0 to A1 and A2. The analysis of these motor units activities suggested that abnormal continence reflex (i.e. failure of vesicourethral and urethrourethral relaxation reflex and exaggeration of urethrourethral contraction reflex) might be contributing to the genesis of DSD.     

Induction of bladder sphincter dyssynergia by kappa-2 opioid receptor agonists in the female rat

PURPOSE: The nonselective kappa opioid receptor agonist ethylketocyclazocine suppresses external urethral sphincter (EUS) reflexes in cats. We examined the role of spinal kappa-opioid receptor subtypes in the control of EUS function in rats using selective kappa-1 (U-50,488) or kappa-2 (GR-89,696) opiate receptor agonists. MATERIALS AND METHODS: Urethane anesthetized female rats were catheterized through the bladder dome for cystometry. EUS function was assessed electromyographically. Drugs were administered intrathecally or intravenously. RESULTS: Micturition in rats is accompanied at different times by tonic (continuous) EUS spike activity and by phasic bursts of spikes separated by pauses. GR-89,696 (0.05 to 5 microg intrathecally) caused a dose dependent decrease in the number of bursts per micturition without affecting spike frequency within individual bursts or during periods of tonic activity. It resulted in decreased voiding efficiency and at high doses dyssynergia and overflow incontinence. The nonselective opiate receptor antagonist naloxone (1 mg/kg intravenously) blocked GR-89,696 effects. U-50,488H (0.05 to 15 microg intrathecally) caused no change in cystometric parameters or in EUS-electromyography. CONCLUSIONS: Efficient voiding in rats depends on a spinal pattern generator causing EUS motor neuron firing to occur in bursts, resulting in rapid urethral contraction and relaxation. Intrathecal kappa-2-opiate receptor agonists suppress this pattern generator, decreasing the number of bursts occurring during each micturition without decreasing motor neuron spike frequency during individual bursts or during tonic spike activity associated with urethral closure. Resultant dyssynergia leads to decreased voiding efficiency. The relevance of kappa-2 opioid receptors should be explored in higher species, especially regarding spinal cord injury induced dyssynergia.