Urinary Contraction Research Articles

Inhibitory effects of a new, potent, centrally acting muscle relaxant, (4S,5R)-4-(2-methylpropyl)-3-[3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-one (NC-1200) on micturition contractions of the bladder in rats

The effect of the centrally acting muscle relaxant, (4S,5R)-4-(2-methylpropyl)-3-[3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-one (NC-1200) on micturition contractions of the urinary bladder was tested in anesthetized rats with the intention of using it clinically to depress vesical micturition contractions. Rhythmic micturition contractions of the bladder were produced by expanding a balloon inserted in the bladder. Efferent nerve activity of the pelvic and hypogastric branches of the bladder was recorded. Both the vesical micturition contractions and the rhythmic burst discharges of the pelvic efferent nerve were inhibited by the i.v. administration of NC-1200 (1–10 mg/kg) in a dose-dependent manner. Hypogastric efferent nerve activity and ganglionic synaptic transmission from the pelvic preganglionic neurons to their postganglionic neurons innervating the bladder were not influenced significantly by the i.v. administration of NC-1200. No inhibitory effect on vesical smooth muscle was observed. From these results we concluded that NC-1200 inhibits the micturition contraction by inhibiting pelvic efferent nerve activity and that this inhibitory effect of NC-1200 originates mainly in the central nervous system.

Tachykinin-like immunoreactivity in the mammalian urinary bladder: Correlation with the functions of the capsaicin-sensitive sensory nerves

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig > mice > rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 μM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and “efferent” functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.

Effect of Age on in Vivo Urinary Bladder Function in the Rat

The effects of age on micturition in male Fischer 344 rats, ages five to seven, 16 to 18 and 22 to 24 months, were studied. The 24hr. water intake, 24hr. urine output, frequency and volume of each micturition were obtained from rats housed individually in metabolic cages. Intravesical pressure and volume at which the micturition contraction occurred were evaluated using natural-fill cystometry. The 24hr. water intake and urine output increased significantly with advancing age; 22 to 24 month rats showed a 39% increase in water intake and a 93% increase in urine output compared to five to seven month rats. The increase in urine output observed in the 22 to 24 month old rats was manifested by a 95% increase in volume per micturition and a 52% increase in frequency of micturition compared to five to seven month old rats. The pressure at micturition (PAM) was 100% greater in 22 to 24 and 16 to 18 month old rats compared to five to seven month old rats with no age-related difference in bladder volume at micturition (BVM). These studies demonstrate that in vivo micturition changes with age in the male F344 rat. Although there were no overt urological dysfunctions observed in the aging rats, the alterations in function would indicate that there were changes in either the mechanisms controlling micturition, or changes in the musculature itself. These possibilities will be the subject of further investigations.

The effect of nifedipine on spontaneous, drug-induced and reflexly-activated contractions of the rat urinary bladder: Evidence for the participation of an intracellular calcium store to micturition contraction

1. The effect of nifedipine on spontaneous and stimulated motility of the rat urinary bladder has been investigated in vitro (isolated detrusor strips) and in vivo (micturition reflex). 2. Nifedipine inhibited tone and spontaneous activity of the isolated rat bladder, its effect being greater in indomethacin-treated preparations. Nifedipine suppressed the KCl induced phasic and tonic contraction and inhibited by 60–80% the carbachol- or ATP- induced contractions. Nifedipine reduced by about 70% amplitude of the nerve-mediated bladder contractions. 3. Exposure to Ca free medium containing EDTA suppressed tone and spontaneous activity of the rat bladder. In these conditions the response to KCl or ATP was rapidly abolished while a response to carbachol was still evident even after a long exposure to the Ca free medium. 4. In vivo, nifedipine affected reflex micturition e.g. increased volume threshold and slightly reduced amplitude of micturition contraction. In addition, nifedipine reduced voiding efficiency e.g. increased residual volume after micturition. These effects were evident following ligation of the ureters because in normal conditions nifedipine induced a marked diuresis which masked its effect on volume threshold. 5. These findings indicate that in the rat urinary bladder Ca from both intra- and extracellular pools is mobilized during spontaneous or stimulated contractions. Mobilization of an intracellular Ca pool by cholinomimetics or other neurotransmitter(s) may be responsible for the nifedipine-resistant component of the voiding contraction in vivo.

Effects of (+/-)-4'-ethyl-2-methyl-3-(l-pyrrolidinyl) propiophenone hydrochloride (HY-770) on the bladder function

The effects of HY-770 on micturition reflexes in rats, dogs and cats and urethral pressure in dogs were compared with those of flavoxate.HC1 (flavoxate), terodiline.HCl (terodiline) and oxybutynin.HCl (oxybutynin). 1) HY-770, in intravenous (2 and 4 mg/kg) and intraduodenal (12.5 and 25 mg/kg) administrations, dose-dependently abolished the rhythmic bladder contractions in anesthetized rats. The activity of HY-770, in intravenous administration (i.v.), was almost equal to those of flavoxate, terodiline and oxybutynin; and the activity of HY-770, like terodiline, was more potent than that of flavoxate in intraduodenal administration (i.d.). 2) In the cystometrograms, HY-770 (3, 4 or 8 mg/kg, i.v.) dose-dependently increased the time to micturition (capacity of bladder) without decreasing the amplitude of micturition contraction in anesthetized rats, dogs and cats, and HY-770 (25 mg/kg, i.d.) also increased the capacity in anesthetized cats. 3) HY-770 (4 and 8 mg/kg, i.v.) dose-dependently increased the capacity of the bladder in the cystometrograms of pollakiuria induced by either transection of both the hypogastric nerves or chronic cannulation to the bladder in anesthetized or conscious rats, respectively. 4) HY-770 (25 mg/kg, i.d.) slightly decreased the urethral pressure in anesthetized dogs. These results suggest that HY-770 is a promising drug for the treatment of pollakiuria induced by a neurogenic bladder or unstable bladder, etc.

Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents

Topical application of exogenous prostanoids (PGE 2, TBX B 2) on the serosal surface of the urinary bladder of urethane-anaesthetized rats activated reflex micturition. Likewise, intravesical instillation of PGE 2 during the cystometrogram lowered the threshold for reflex micturition. Both effects were prevented by systemic capsaicin desentization (50 mg/kg s.c., 4 days before). Indomethacin pretreatment and systematic capsaicin desensitization each increased the micturition threshold without affecting the amplitude of micturition contraction. However, the effect of the two treatments combined was not greater than the effect of either alone. These findings support the idea that endogenous prostanoids facilitate reflex micturition by stimulating or sensitizing, directly or indirectly, the subset of bladder mechanoreceptors which is capsaicin-sensitive in adult rats.

Neuroeffector mechanisms in the voiding cycle of the guinea-pig urinary bladder.

1. The effect of drugs expected to modify cholinergic (atropine, physostigmine) or GABA-ergic (GABA, picrotoxin, bicuculline methiodide, BMI) neurotransmission were investigated on the voiding cycle of the urinary bladder in urethane-anaesthetized guinea-pigs. 2. Transvesical saline infusion elicited a series of regular voiding cycles which were abolished by topical tetrodotoxin as well as by topical or intravenous (i.v.) hexamethonium, thus indicating their reflex neurogenic origin. 3. Either i.v. or topical atropine decreased amplitude and duration of micturition contraction, reduced efficiency of bladder voiding and, in about 30% of preparations, suppressed micturition (overflow incontinence). Either topical or i.v. physostigmine potentiated, in an atropine-sensitive manner, voiding efficiency. 4. GABA was administered during the ascending limb of the voiding cycle: i.v. GABA inhibited while topical GABA increased efficiency of the first voiding cycle. Both direction and intensity of the effect of GABA were dependent upon initial pressures. The second and following voiding cycles after GABA administration were inhibited transiently. 5. Either topical or i.v. picrotoxin or BMI potentiated the efficiency of the voiding cycle of the guinea-pig bladder. In these preparations either i.v. or topical GABA (administered during the ascending limb of the voiding cycle) produced only inhibitory effects on voiding efficiency. 6. These findings indicate that, in guinea-pigs, bladder voiding is largely dependent upon an intact cholinergic neurotransmission. Although amplitude of the initial voiding contraction is largely atropine-resistant, its duration and, consequently, degree of bladder voiding, are strongly influenced by blockade (atropine) or potentiation (physostigmine) of cholinergic neurotransmission. Endogenous GABA-ergic mechanism modulate, possibly at peripheral level, the voiding efficiency of the guinea-pig bladder. GABA exerts a complex neuromodulatory influence on voiding function, its overall effect being mainly influenced by resting parameters.

Differential antagonism of mu agonists by U50,488H in the rat

Agonist, and antagonist effects of the proposed kappa opioid agonist, U50,488H (U50) have been studied in an experimental model of seizure activity (flurothyl-induced seizure threshold) (ST) and in the central modulation of spontaneous, volume-induced micturition contractions (bladder motility) (BM) in rats. Intracerebroventricular (i.c.v.) administration of U50 (at the doses tested) did not produce any agonist effect in either ST or in BM. In contrast, i.c.v. administration of [D-Ala 2, NMPhe 4, Gly-o1]enkephalin (DAGO) or etorphine, agonists with activity at mu opioid receptors, produced an elevation of ST and inhibition of BM. The elevation in ST produced by etorphine (0.004 nmol) was prevented by prior treatment with U50. In contrast, the approximately equieffective elevation in ST resulting from DAGO was not affected by U50 pretreatment. Similarly, pretreatment of rats with U50 antagonized the approximately equieffective BM effects of etorphine, but not those of DAGO. As both DAGO and etorphine are thought to exert their effects via the opiate mu receptor, the results may be consistent with the view that subpopulations of mu receptors exist within the central nervous system; these sites may be differentially associated with the kappa receptor.

The correlation between sensory-efferent functions mediated by the capsaicin-sensitive neurons and substance P content of the rat urinary bladder

The substance P-like immunoreactivity (SP-LI) of the urinary bladder of adult rats was depleted by capsaicin desensitization (50 mg/kg, s.c., 4 days before) or extrinsic denervation (pelvic ganglionectomy) thus indicating its neurogenic sensory origin, SP-LI levels were inversely proportional to the volume threshold for micturition but not to the amplitude of micturition contraction. Moreover SP-LI levels were directly related to the amplitude of the capsaicin- but not field stimulation-induced contraction of the rat isolated bladder. These findings indicate that the SP-LI level of the rat bladder is a useful index for monitoring the dual sensory-efferent functions of the capsaicin-sensitive innervation of this organ.

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy.

The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of 'in vivo' cystometry and 'in vitro' recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. After 7-9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 'In vitro' experiments indicated that the response to field stimulation (0.1-20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e.g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accommodation of greater than normal volumes with similar increase of intraluminal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals

Normal healthy visceral tissue is largely insensitive to many kinds of tissue damaging stimuli, such as cutting, crushing or burning. When inflamed, however, visceral tissue frequently and easily elicits pain. Here we have produced inflammatory responses in urinary bladders of chronically decerebrated rats with irritant chemicals, as a model of a visceral pain state. The irritants used were 25% turpentine, 2.5% mustard oil, 2% croton oil. All produced a strong inflammatory response, as judged by protein extravasation and oedema, and invasion of the tissue with leucocytes, which started within hours of treatment. The inflammatory states were associated with hyperexcitable bladder reflexes; baseline pressures were larger at given volumes, and large micturition contractions occurred at lower volumes. These changes persisted for up to 48 h after a single treatment. The behaviour of the animals and their responsiveness to noxious stimulation were also assessed. In general animals were hypersensitive to noxious stimuli applied to the tail or caudal abdomen, with small or no changes in responses to hind limb or rostral abdominal stimulation. These irritants, particularly turpentine, applied to chronic decerebrate rats may thus provide useful models for studies of the neuronal processes which contribute to visceral nociception.

Plasma extravasation in the rat urinary bladder following mechanical, electrical and chemical stimuli: evidence for a new population of chemosensitive primary sensory afferents

In the skin activation of unmyelinated primary afferents produces vasodilation and plasma extravasation. Here, using Evans blue dye leakage, we have quantitatively compared the ability of mechanical, chemical and electrical stimulation of afferents to produce extravasation in the urinary bladder of anaesthetized rats. Mechanical stimulation - a series of large active contractions of vesical smooth muscle induced by maintained distension - elicited no increase in extravasation compared to controls. In contrast, a similar period of electrical stimulation of nerves supplying the bladder, or chemical stimulation with intravesical instillation of mustard oil, produced high levels of extravasation. We conclude that afferents activated during distension and micturition contractions are different from those which produce extravasation. The latter may be important in pathophysiological cases such as inflammation of the urinary bladder.

The role of the capsaicin-sensitive innervation of the rat urinary bladder in the activation of micturition reflex.

Capsaicin applied on the serosal surface of the urinary bladder in urethane-anaesthetized rats produces two distinct types of motor effects: a tetrodotoxin-, hexamethonium- and lidocaine-insensitive 'tonic' contraction and a series of tetrodotoxin-, hexamethonium- and lidocaine-sensitive rhythmic contractions. Both 'tonic' and rhythmic contractions are abolished by bladder denervation indicating their neurogenic origin. The rhythmic but not the 'tonic' component of the contractile effect of capsaicin is abolished by spinal cord transection indicating activation of a supraspinal micturition reflex. The motor effects of topical capsaicin are unaffected by pretreatment with indomethacin or diphenhydramine plus cimetidine. Pretreatment with a large dose of subcutaneous (SC) capsaicin increases both volume and pressure threshold for micturition while amplitude of micturition contraction is unaffected. Moreover the spinal somatovesical reflex elicited by pinching of the perineal skin is unaffected by capsaicin-desensitization. The intracerebroventricular (ICV) administration of capsaicin reproduces the effects of SC capsaicin on the bladder response to saline filling. Rats pretreated with ICV capsaicin are as sensitive as controls in reacting to noxious heat (hot plate test) while the wiping response to instillation of capsaicin into one eye was abolished. These findings provide functional evidence for the presence in the rat urinary bladder of a capsaicin-sensitive innervation which subserves a sensory function in relaying volume/pressure information from detrusor muscle to central nervous system. Information carried through these capsaicin-sensitive fibers appears to be relevant for initiation of a supraspinal vesico-vesical micturition reflex. Functional evidence indicates that these fibers may terminate at supraspinal level.

The Effect of Capsaicin Pretreatment on the Cystometrograms of Urethane Anesthetized Rats

Administration of capsaicin to newborn rats produced a slight but significant increase in bladder weight and markedly altered the cystometrograms of urethane anesthetized rats. In particular capsaicin pretreatment significantly increased micturition threshold. In many of these preparations the bladders exhibited a hypertonic response to saline filling; the flat phase of the cystometrogram as not observed. Capsaicin pretreatment of adult animals increased micturition threshold up to 1 month from capsaicin administration. In these preparations a flat volume-pressure relationship receded micturition contractions. Administration of capsaicin to both newborn and adult animals did not alter the amplitude of micturition contractions. Intravesical nstillation of capsaicin had an cute excitatory effect on the responsiveness of the urinary bladder to reflex activation.These findings indicate that capsaicin pretreatment produces a functional impairment of the ensory branch of micturition reflexes and suggest that a capsaicin-sensitive mechanism(s) is nvolved in the regulation of micturition threshold.

Regulation of Urinary Bladder Capacity by Endogenous Opioid Peptides

Naloxone administered to chloralose or ketamine anesthetized cats reduced urinary bladder capacity. Successive cystometrograms revealed that naloxone in doses of 0.5μg./kg. to 15μg./kg. i.v. reduced the volume necessary to evoke micturition by 10 to 50 per cent, respectively. The effect was maximal within a few minutes, remained constant for about ½ hour and returned to control values over the next 2 to 3 hours. Following return to control, subsequent doses of naloxone produced no further effect on capacity. In chloralose anesthetized animals naloxone also increased the frequency and amplitude of low amplitude pressure waves on the tonus limb of the cystometrogram. Intrathecal administration of naloxone to the sacral spinal cord did not significantly reduce the volume necessary to evoke micturition even at large doses, but did increase the amplitude of micturition contractions. These data, along with previous reports, suggest that mu receptors in the brainstem alter urinary bladder capacity, while delta receptors in the spinal cord modulate the magnitude of bladder contractions. Pharmacological manipulation of these receptor systems could provide a tool for the management of neurogenic bladder dysfunction.

Urethral Response During Bladder Contraction Induced by Subcutaneous Bethanechol Chloride: Elicitation of a Sympathetic Reflex Urethral Constriction

The responses of the urethra to bladder filling and to subcutaneous bethanechol were studied in a surgically separated bladder-urethra preparation in chloralose anesthetized cats. With the pudendal nerves cut or the neuromuscular junction blocked with gallamine, urethral closure pressure increased during bladder filling and the initial phase of the micturition contraction. It then fell spontaneously or in response to bladder emptying through a vent. With the bladder volume held constant subcutaneous bethanechol induced an increase in basal bladder pressure which culminated in a sustained (reflex) contraction. The urethral constrictor response resembled that seen during the cystometrogram; an increase during the rise in detrusor pressure and a fall during the latter part of the sustained (reflex) contraction. In both cases the urethral response was substantially depressed by hypogastric nerve transection or by intravenous prazosin, implying that the urethral responses were reflexly mediated through the sympathetic system. Intra-arterial bethanechol also produced a urethral constriction, but this response was abolished by atropine and not affected by hypogastric nerve section or prazosin. It is therefore concluded that although bethanechol can produce urethral constriction through a direct muscarinic action on the urethra, it does not do so after subcutaneous administration in a neurally intact cat. The urethral response seen after subcutaneous bethanechol administration is part of the micturition reflex complex and is sympathetically mediated.

Somato-vesical reflexes in chronic spinal cats

The effects of afferent volleys in hindlimb cutaneous and muscle nerves on vesical tone and contractility and on the discharges in pelvic nerves to the bladder were measured in anesthetized CNS-intact and 2–19 months chronic spinal cats. In chronic spinal cats volleys in group III and IV fibers increased the tone of the quiet, empty bladder (excitatory somato-vesical reflex). The same volleys inhibited the slow, large, rhythmic micturition contractions of the expanded bladder (inhibitory somato-vesical reflex). In CNS intact cats single or short tetanic volleys induced a reflex discharge in pelvic vesical nerve branches with 3 distinct components. These reflexes could be observed during micturition contractions, not markedly between the contractions or when the bladder was empty and quiet. The latencies of the 3 components were 90, 320 and 770 ms, respectively. The two early components (A1- and A2-reflex) were evoked by volleys in group II and III hindlimb afferents. The late component (C-reflex) was induced by group IV volleys. In chronic spinal cats a group II and III-induced A-reflex (latency 90 ms) and a group IV-induced C-reflex (latency 340 ms) were observed. The central pathways and the physiological significance of the various somato-vesical reflexes are discussed.

The Neurophysiological Basis of Bladder Inhibition in Response to Intravaginal Electrical Stimulation

Intravaginal electrical stimulation (IVS) induces a profound bladder inhibition and is successful in the treatment of incontinence due to detrusor instability. In this experimental study in cats, direct recordings of the efferent activity in thin hypogastric and pelvic nerve filaments to the bladder were used to analyze the neuronal mechanisms underlying this bladder inhibition. A longlasting reflex discharge, with a latency of 35 to 50msec., was evoked in the hypogastric nerve by IVS. The reflex discharge was unaffected by imposed changes in intravesical pressure or by micturition contractions, but the response was very frequency-sensitive with an optimal transmission at about 5Hz of stimulation. A “spontaneous” efferent activity could be recorded in the pelvic nerve filaments when the bladder pressure was elevated above 5 to 7cm. H2O. The pelvic activity occurred in 10 to 20-second bursts, each followed by an abortive detrusor contraction. IVS of 5 to 10Hz completely abolished this efferent pelvic activity by central inhibition. The findings are discussed in relation to the normal neuronal control of the bladder and to the clinical application of IVS.

Reflex bladder activity induced by electrical stimulation of hind limb somatic afferents in the cat

Methods used and results obtained in a study of reflex responses of the bladder were as follows. Intravesical pressure was recorded continuously by the balloon method in chloralose—urethane anaesthetized cats. Various afferent fibres of hind limb cutaneous and muscle nerves were stimulated electrically, and the resulting changes in vesical functions were examined. It was found that: (1) when the bladder was nearly empty and quiescent, repetitive stimulation of group III (thin myelinated) and IV (non-myelinated) cutaneous or muscle afferent fibres of hind limb nerves caused a reflex increase in the vesical tonus. This somato-vesical excitatory reflex was propriospinal with its efferent arc mainly in the pelvic nerves; (2) when there were spontaneous, large (amplitude above 300–400 mm H 2O), rhythmic (about 1.0–2.5/min) micturition contractions of the expanded bladder, these contractions were inhibited by repetitive stimulation of the group III and IV cutaneous or muscle afferent fibres of hind limb nerves. The inhibition was sometimes followed by subsequent larger micturition contractions. The efferent arc for this somato-vesical inhibitory reflex was also in the pelvic nerves. Supraspinal structures were essential for producing the micturation contractions; (3) stimulation of group III and IV afferent fibres together was more effective than stimulation of the group III afferent fibres alone in activating either the excitatory or inhibitory somato-vesical reflex pathways.

Effects on reflex bladder activity of chemical stimulation of small diameter afferents from skeletal muscle in the cat

In anesthetized cats selective activation of fine muscle afferents of the hindlimb by KCl or bradykinin (Brad.) induced reflex changes in the urinary bladder. The nature of the reflex responses depended on the functional state of the bladder: they were excitatory when the bladder was quiescent and inhibitory during large, slow, rhythmic micturition contractions. Selective activation of large muscle primary afferents by succinylcholine was ineffective. All reflexes disappeared after cutting the sciatic or the pelvic nerves. Transection of the hypogastric nerves to the bladder had no effect.