Preliminary observations of a synergistic bladder-sphincter relationship following spinal cord injury in a quadruped animal

BACKGROUND/OBJECTIVES: High urethral resistance or detrusor-sphincter dyssynergia (DSD) is characterized by obstructed voiding during bladder contractions. DSD is caused by an exaggerated pelvic floor reflex resulting from sensory input from elevated pressure in the bladder that produces reflex constriction of the urethral sphincter. The objective of this study was to determine whether sensory input from the bladder produced synergistic or dyssynergic pelvic floor reflexes following SCI in an animal model. METHODS: A pelvic floor reflex that shares the same motor pathway with DSD is the bulbocavernosus (BC) reflex. The BC reflex was elicited with electrical stimulation in 4 male cats with T1 spinal injury, and recorded as an anal sphincter contraction. Recordings were obtained during control and elevated bladder pressures. Increased bladder pressure was induced with either manual pressure (Crede procedure) or spontaneous contractions resulting from bladder filling. RESULTS: During the control period, the BC reflex indicated by the peak anal pressure response was 23 +/- 6 cmH2O. During elevated bladder pressure of 34 +/- 18 cmH2O, the BC response decreased to 10 +/- 3 cmH2O (not significant), showing a synergistic relationship. Anal sphincter tone between BC reflex tests showed a dyssynergic response. All 4 animals showed increased tone during elevated bladder pressures that averaged 9 +/- 5 cmH2O. Because abdominal pressure was not recorded, the significance is not clear. However, there was further support of a dyssynergic relationship based on increases in the anal and urethral electromyography recordings and some pelvic floor spasms during the elevated bladder pressure. CONCLUSIONS: Because 2 different pelvic floor activities were observed during increased bladder pressures, this animal model may be described best as a mixed model. This model shows both synergistic and dyssynergic relationships between the bladder and the BC contractions. Although observed changes were not significant, the unique observations of synergistic bladder-sphincter activity shown by the inhibited BC reflex is in marked contrast to the strictly dyssynergic bladder-sphincter relationship seen in SCI patients.     

Preliminary Observations Of A Synergistic Bladder-Sphincter Relationship Following Spinal Cord Injury In A Quadruped Animal

Abstract

Background/Objectives: High urethral resistance or detrusor-sphincter dyssynergia (DSD) is characterized by obstructed voiding during bladder contractions. DSD is caused by an exaggerated pelvic floor reflex resulting from sensory input from elevated pressure in the bladder that produces reflex constriction of the urethral sphincter. The objective of this study was to determine whether sensory input from the bladder produced synergistic or dyssynergic pelvic floor reflexes following SCI in an animal model.

Methods: A pelvic floor reflex that shares the same motor pathway with DSD is the bulbocavernosus (BC) reflex. The BC reflex was elicited with electrical stimulation in 4 male cats with T1 spinal injury, and recorded as an anal sphincter contraction. Recordings were obtained during control and elevated bladder pressures. Increased bladder pressure was induced with either manual pressure (Crede procedure) or spontaneous contractions resulting from bladder filling.

Results: During the control period, the BC reflex indicated by the peak anal pressure response was 23 ± 6 cmH20. During elevated bladder pressure of 34 ± 18 cmH20, the BC response decreased to 10 ± 3 cmH20 (not significant), showing a synergistic relationship. Anal sphincter tone between BC reflex tests showed a dyssynergic response. All4 animals showed increased tone during elevated bladder pressures that averaged 9 ± 5 cmH2 0 . Because abdominal pressure was not recorded, the significance is not clear. However, there was further support of a dyssynergic relationship based on increases in the anal and urethral electromyography recordings and some pelvic floor spasms during the elevated bladder pressure.

Conclusions: Because 2 different pelvic floor activities were observed during increased bladder pressures, this animal model may be described best as a mixed model. This model shows both synergistic and dyssynergic relationships between the bladder and the BC contractions. Although observed changes were not significant, the unique observations of synergistic bladder-sphincter activity shown by the inhibited BC reflex is in marked contrast to the strictly dyssynergic bladder-sphincter relationship seen in SCI patients.     

Evoked response of the bulbocavernosus reflex.

The bulbocavernosus reflex can be elicited either by penile or urethral stimulation. The mean signal transit time after electrostimulation of the dorsal penile nerve to evoked response in the anal sphincter (35 msec) was only half the signal transit time after stimulation in the posterior urethra (60 msec). Thus, the modified bulbocavernosus reflex elicited either by squeezing the glans penis or by pulling a urethral balloon catheter represents two different reflexes with differenct afferent and probably different intraspinal pathways. In the clinic it is therefore important, when testing the bulbocavernosus reflex, to report how it is elicited.     

Differential effects of activation of peripheral and spinal tachykinin neurokinin(3) receptors on the micturition reflex in rats

PURPOSE: We clarified the roles of tachykinin neurokinin (NK)3 receptors in the bladder or spinal cord for control of the micturition reflex in rats. MATERIALS AND METHODS: In female rats under urethane anesthesia repetitive bladder contractions were elicited by saline infusion into the bladder through intravesical bladder catheters. The effects of peripheral receptor activation were first examined by topical application of the tachykinin NK3 receptor agonist [MePhe]-NKB (Calbiochem, Darmstadt, Germany) in normal rats and rats pretreated with capsaicin (Sigma Chemical Co., St. Louis, Missouri) 4 days before the experiments. Subsequently the effects of spinal NK3 receptor activation were examined by intrathecal administration of [MePhe]-NKB via implanted intrathecal catheters. The effects of the tachykinin NK3 receptor antagonist SB235375 and the opioid receptor antagonist naloxone on changes in bladder activity induced by [MePhe]-NKB were also investigated. RESULTS: Topical application of [MePhe]-NKB onto the bladder surface decreased intercontraction intervals and bladder capacity, and increased baseline bladder pressure in dose dependent fashion. [MePhe]-NKB induced bladder overactivity was inhibited by simultaneous topical administration of SB235375 or by capsaicin pretreatment. In contrast, intrathecal injection of [MePhe]-NKB increased intercontraction intervals in dose dependent fashion and at a high dose it induced overflow incontinence or inefficient voiding. These inhibitory effects of [MePhe]-NKB in the spinal cord were antagonized by the intrathecal injection of SB235375 or naloxone. CONCLUSIONS: These results indicate that the tachykinin NK3 receptor mediated neural control of the micturition reflex has dual actions depending on the location of receptor activation. Activation of tachykinin NK3 receptors located in the bladder can induce bladder overactivity at least in part via the activation of capsaicin sensitive C-fiber afferents, while tachykinin NK3 receptor activation in the spinal cord can inhibit the micturition reflex through an opioid mechanism.     

Autonomic neuropathy in BB rats and alterations in bladder function

In vivo urinary bladder function was examined in BB rats after 4 and 6 mo of diabetes, and the data were correlated with morphometric changes in the pelvic and hypogastric nerves, which constitute the micturition reflex arc. After controlled bladder distension, diabetic animals revealed irregular bladder contractions at frequencies that were reduced to 33% of normal values and with significantly increased amplitudes. The abnormal micturition in diabetic animals was elicited at moderately elevated threshold volumes. These functional abnormalities of the diabetic bladder were associated with a progressive axonopathy of afferent myelinated sensory fibers and later-occurring axonal atrophy of unmyelinated efferent preganglionic fibers. These data suggest that diabetic urinary bladder dysfunction is initiated by a visceral sensory neuropathy involving the afferent limb of the micturition reflex arc.     

Contraction of gluteal maximus muscle on increase of intra-abdominal pressure: role in the fecal continence mechanism

The gluteus maximus muscle (GMM) appears to contract with increased intra-abdominal pressure (IAP). The hypothesis that GMM contraction with increased IAP was investigated. The study comprised 32 healthy volunteers. IAP was measured by intravesical catheter. The response of electromyography of the GMM and external anal sphincter to sudden momentary and slow sustained straining was registered. The procedure was repeated after individual urinary bladder and GMM anesthetization. Sudden straining increased electromyographic activity of the external anal sphincter and GMM. Slow, sustained straining raised electromyographic activity of the gluteus maximus and external sphincter at differing degrees depending on straining intensity. The anesthetized gluteus maximus or urinary bladder did not respond to straining. The suggested GMM contraction on straining seems mediated through a reflex that is called "straining-gluteal reflex." This reflex appears to assist anal closure through extended and laterally rotated femur induced by gluteus contraction.     

Neural control of internal anal sphincter function

The effect on anal tone of electrical stimulation of the presacral (hypogastric) sympathetic nerves has been studied in eight patients during abdominal rectopexy or restorative proctocolectomy. A sharp fall in anal pressure occurred in seven patients (mean fall 59 cmH2O; range 35-80 cmH2O). In one patient given a beta- and alpha-sympathetic blocking drug (labetalol 200 mg) intra-operatively, the anal pressure decreased by 15 cmH2O. These observations show that stimulation of the presacral sympathetic nerves causes relaxation of the internal anal sphincter and implies that these nerves may induce relaxation of the sphincter in vivo. The pathway of the recto-anal reflex has been studied intra-operatively in three patients undergoing rectal excision. The recto-anal reflex is present after presacral nerve blockade and after full mobilization of the rectum, but is abolished by circumferential rectal myotomy. The reflex has a local intramural pathway. This observation validates the assumption that absence of this reflex is a feature of aganglionosis, as in Hirschsprung's disease.     

Effects of a selective metabotropic glutamate receptor agonist on the micturition reflex pathway in urethane-anesthetized rats

AIMS: To determine a possible role of metabotropic glutamate receptors in the spinobulbospinal micturition reflex pathway in the rat. MATERIALS AND METHODS: A selective metabotropic glutamate receptor agonist, trans-(+/-)-1-amino1,3-cyclopentanedicarboxylic acid (trans-ACPD) was administered to the lumbosacral spinal cord via an intrathecal catheter in urethane anesthetized rats. Amplitude of reflex bladder contractions evoked by bladder distension under isovolumetric condition as well as amplitude of bladder contractions elicited by electrical stimulation of the pontine micturition center (PMC) were examined before and after administration of trans-ACPD. The effect of trans-ACPD on the urethral activity during isovolumetric bladder contractions was also examined by monitoring urethral perfusion pressure and electromyography of the external urethral sphincter (EUS-EMG). RESULTS: Trans-ACPD (3-10 microg) completely inhibited reflex bladder contractions evoked by bladder distension and the duration of inhibition was dose dependent (3 microg: 11.4 +/- 2.8 min, 5 microg: 13.2 +/- 1.3 min, 10 microg: 36.2 +/- 2.4 min). The mean amplitude of bladder contractions evoked by electrical stimulation of the PMC was reduced to 12.6 +/- 2.3% of control by 10 microg of trans-ACPD. In addition, bursting activity of EUS-EMG and corresponding high frequency oscillations of urethral pressure during isovolumetric bladder contractions were completely abolished by 10 microg of trans-ACPD. CONCLUSIONS: These results indicate that intrathecal administration of a selective metabotropic glutamate receptor agonist to the lumbosacral spinal cord has an inhibitory effect on the spinobulbospinal micturition reflex pathway in urethane-anesthetized rats. This pharmacological action is attributed at least to the inhibitory effect on the descending pathway from the PMC to the lumbosacral spinal cord.     

Clinical and neurophysiologic testing of the penilo-cavernosus reflex

AIMS: Both clinical and neurophysiologic testing of the penilo-cavernosus reflex is used in clinical practice. The aim of the present study was to determine the as yet unestablished potential contribution of sacral reflex testing to the diagnostic evaluation of patients with suspected neuropathic sacral lesions. METHODS: Fifty-three men with clinical, electrodiagnostic, and radiologic signs of chronic cauda equina or conus medullaris lesions were studied. Clinical examination, including assessment of anal sphincter tone and perianal sensation, and both clinical and neurophysiologic testing of the penilo-cavernosus reflex, were performed. The sacral reflex was elicited on a single (normal latency: <39.4 msec) and double (<36.0 msec) electrical, and on mechanical stimulation (<35.5 msec). Responses were recorded by a concentric needle electrode inserted consecutively into the left and right bulbocavernosus muscles. The response from the more abnormal side was further analyzed. RESULTS: Clinical testing of the penilo-cavernosus reflex was abnormal in 81% of patients with normal anal squeeze, in 78% with normal perianal sensation, and in 50-67% with bilaterally normal neurophysiologic findings on three different stimulation techniques. Neurophysiologic testing of the reflex was abnormal in 69-94% of patients with normal anal squeeze, in 56-67% with normal perianal sensation, and in 44-67% of patients with a clinically normal reflex. CONCLUSIONS: The study supported the clinical utility of both clinical and neurophysiologic measurement of the penilo-cavernosus reflex.     

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.     

Dynamic Bulbocavernosus Reflex: Dyssynergia Evaluation Following SCI

ABSTRACT

High urethral resistance caused by detrusor-sphincter dyssynergia (DSD) occurs following spinal cord injury (SCI) and results in poor voiding. A major pelvic floor reflex that may be involved in DSD is the bulbocavernosus reflex (BC) and evaluation of this reflex during the micturition cycle may provide additional information regarding this role. The periodic BC observed during micturition via cystometry is described as a dynamic bulbocavernosus reflex (DBC).

The DBC was induced in upper motor neuron SCI patients using periodic dorsal penile nerve stimulation; the evoked reflex response was recorded with an anal sphincter pressure sensing balloon. Stimulation of 15–50 mA was applied at the base and dorsal side of the penis with surface electrodes, pulsed at a rate of 0.25 Hz. By applying the stimulation during cystometry, the BC reflex could be evaluated throughout the entire micturition cycle. Results showed that the DBC increased during bladder filling and bladder contractions. These findings indicate that an enhanced BC reflex is a major factor causing increased urethral resistance during micturition. (J Am Paraplegia Soc: 17; 140–145)     

Dissociation of urethral and anal sphincter activity in neurogenic bladder dysfunction.

In 53 patients with suspected neurogenic bladder dysfunction carbon dioxide cystometry was done in combination with urethral and anal sphincter electromyography. Complete dissociation between the reflex activity of the 2 sphincters was found in 25 per cent of the patients and only 58 per cent of the patients had identical reflex activity. It is concluded that anal sphincter electromyography is highly unreliable in the diagnosis of urethral sphincter dysfunction.     

Peripheral neurology as a predictor of bladder dysfunction in congenital neuropathic bladder

Urodynamic findings and peripheral neurology were correlated in 62 patients with myelomeningocele. The primary motor and sensory levels bore no relation to bladder dysfunction. The ano-cutaneous reflex was a useful predictor, in that where the reflex was positive there was likely to be detrusor hyper-reflexia, a competent bladder neck and absence of sphincter weakness leakage. Where the reflex was absent, detrusor hyper-reflexia was absent or mild, the bladder neck usually incompetent and sphincter weakness leakage common. (Detrusor compliance could not be predicted from peripheral neurological findings). We consider the ano-cutaneous reflex to be a useful indication of bladder dysfunction and urodynamic studies are often unnecessary when it is positive.     

Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury

AIMS: Although electrical stimulation of the pudendal nerve has been shown to evoke reflex micturition-like bladder contractions in both intact and spinalized cats, there is little evidence to suggest that an analogous excitatory reflex exists in humans, particularly those with spinal cord injury (SCI). We present two cases where electrical activation of pudendal nerve afferents was used to evoke excitatory bladder responses. SUBJECTS AND METHODS: A percutaneously placed catheter electrode was used to electrically stimulate the pudendal nerve trunk in two males with SCI. The response was quantified with recorded changes in detrusor pressure and EMG activity of the external anal sphincter. RESULTS: In both individuals, frequency specific (f = 20-50 Hz) activation of the pudendal nerve trunk evoked excitatory bladder contractions that also depended on the stimulus amplitude and bladder volume. CONCLUSION: The results suggest that selective activation of the perineal branches of the pudendal nerve may further augment the excitatory reflex evoked by electrical stimulation.     

Minimally-invasive electrical stimulation of the pudendal nerve: a pre-clinical study for neural control of the lower urinary tract

AIMS: Electrical stimulation of afferent pudendal nerve fibers can evoke sustained bladder contractions (SBC) in cats, yet evidence of therapeutic efficacy in human subjects is lacking. This pre-clinical study was undertaken to test the hypothesis that robust bladder contractions can be generated with a minimally-invasive needle electrode. MATERIALS AND METHODS: In seven adult cats, triggered electromyographic (EMG) signals from the external anal sphincter (EAS) were used to minimize the needle-to-nerve distance; while reflex bladder contractions were recorded as 20-sec trains of current pulses of varying amplitude (threshold to 10 mA) and frequency (1-100 Hz) were applied to the nerve. This stimulation paradigm was repeated at successively greater needle-to-nerve distances (0.5 cm intervals) and also at different electrode positions along the nerve. RESULTS: Electrophysiological access to the pudendal nerve was consistently achieved, as indicated by the average threshold for EAS activation (0.31+/-0.19 mA). Using different combinations of stimulus amplitude and frequency, robust SBCs were evoked in every experiment. More rostral electrode positions exhibited stimulation amplitudes and corresponding maximum bladder pressures (0.68+/-0.36 mA and 25.3+/-3.5 cmH2O, respectively) that were comparable to those of more invasive stimulation methods. CONCLUSIONS: The needle electrode provides a minimally-invasive approach that will enable the study of reflexes mediated by pudendal afferents in humans, and allow pre-operative testing before implanting a permanent device.     

Electrical sphincter stimulation in the treatment of detrusor hyperreflexia of paraplegics

Strong anal stimulation at the onset of the vesical pressure increase during an uninhibited bladder contraction prevented further bladder pressure increase and urine loss in 11 out of 15 paraplegics; 5 Hz, 10-Hz and 20—Hz stimuli were equally effective. This effect is probably a spinal reflex. In the acute experiments, stimulation of the peroneal or anterior tibial nerve was without effect on bladder pressure.     

Experimental models of reflex contractile activity in the rabbit bladder

We were able to produce two highly reproducible experimental models (in the rabbit) that demonstrated a high degree of reflex bladder contractile activity. In one model, a somatovesical reflex was induced by touching or pinching the perineal area. This reflex may be organized through a neurogenic reflex at the spinal level. In another model, rhythmic bladder contractions were produced by distal urethral constriction in the absence of bladder distension. These rhythmic contractions were thought to be due to a supraspinal reflex. In both types of contractile reflexes, intravenous administration of hexamethonium inhibited the reflex contractile activity virtually completely, intravenous atropine inhibited over 90% of the induced contractile activity, thus suggesting that these contractions were mediated reflexly through cholinergic stimulation. These two models of reflex bladder contractions should be useful for the study of hyperreflexic bladders.     

肛瘘切开悬浮挂线术对肛管直肠压力和肛门功能影响的临床观察

为了探讨肛瘘切开悬浮挂线术治疗复杂性肛瘘的临床疗效,对采用肛瘘切开悬浮挂线术（47例,治疗组）与肛瘘切开引流术（21例,对照组）治疗的68例患者手术前后直肠肛门反射（RAR）、肛管最大收缩压（AMCP）、肛管最长收缩时间（AL—CT）、肛管静息压（ARP）、直肠静息压（RRP）进行测定,并进行对比分析。结果显示,68例肛瘘患者术后RRP和ARP较术前明显降低;治疗组ARP和AMCP较对照组明显增高,ALCT较对照组明显延长。结果表明,肛瘘手术对肛管功能有不同程度的影响,肛瘘切开悬浮挂线术优于肛瘘切开引流术,对肛管直肠功能影响较小,能更好地保护肛门功能。     

Urinary urgency and reflex incontinence

Urge and reflex incontinence are caused by detrusor dysfunction:urgency may be due to hyperactivity or hypersensitivity of the bladder. Neurogenic hyperactivity of the detrusor is called detrusor hyperreflexia: the neurogenic uninhibited bladder is caused by incomplete, and the so-called reflex bladder by complete, suprasacral lesions. The pathophysiology of symptomatic and idiopathic detrusor hyperactivity and the therapeutic armentarium are described. Bladder drill together with biofeedback and pharmacotherapy with spasmolytic drugs - several potent spasmolytic drugs with different modes of action are available - are the basis of treatment for hyperactivity and hypersensitivity of the detrusor. An alternative is electrostimulation: stimulation of the afferents of the pudendal nerve, via the pelvic floor (anal, vaginal), percutaneously (dorsal nerve of the penis, clitoric nerve) or by the implantation of electrodes results in inhibition of the detrusor. Most (80-90%) patients can be treated successfully by conservative means. Operative measurements comprise bladder denervation and bladder augmentation. The results of bladder denervation by transtrigonal phenolization of the pelvic plexus are highly controversial. In patients with uncontrollable hyperactivity of the detrusor, augmentation of the bladder (e.g. clam ileocystoplasty) is the method of choice, while for those with uncontrollable hypersensitivity of the detrusor, cystectomy followed by bladder substitution should be performed as a last resort. Treatment for urinary incontinence due to detrusor hyperreflexia must be selected bearing in mind that bladder emptying is inadequate, in most cases because of dyssynergia between detrusor and external sphincter. Therapy is basically aimed at transforming hyperreflexia of the detrusor into hyporeflexia, primarily by potent spasmolytic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nomenclature of neurogenic bladder

Vesicourethral physiology is reviewed briefly in the light of recent developments. The effect on bladder function of central nervous system disorders is considered and attention is drawn to the desirability of diverting interest from the bladder to the urethra in neuropathic cases. It is concluded that there are only two basic types of neuropathic bladder function — in lesions of and above the sacral reflex pathways, respectively. Neurologically these are classified according to the condition of the anal and bulbocavernosus reflexes and the ice water test.