0()22-F.34 //87/13'?:2-024CS0'.2.00/0
Vol.
THE ,]OUI{NAL CF UROLOG"'!'
Copyright(~ 1987 by The ·vVilliarns
VVilkins Co.
MEASUREMENT
P,·inted
Feb::-uary
US A.
TRIGONAL SENSITIVITY AS A TEST OF BLADDER FUNCTION LESTER A. KLEIN
From the Harvard Program in Urology (Longwood Area), and Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts
ABSTRACT
A method has been developed for the measurement of sensory receptors that respond to pressure at the base of the bladder and posterior urethra. The application of force to a balloon catheter placed at that part of the bladder regularly results in an urge to urinate. People with normal voiding perceive the urge to void when 245 ± 4 7 gm. (standard deviation) of force are applied. Patients with irritative symptoms (urinary frequency and urgency) perceive the urge to void when 132 ± 50 gm. (p equals 0.0003) are applied. After enucleative prostatectomy more force is required to cause the urge to void (344 ± 48 gm., p equals 0.0003) and even more force is required after radical prostatectomy (469 ± 54 gm., p equals 0.0002). Patients with acute urinary retention or urinary stress incontinence were not distinguishable from the normal group. Patients with chronic urinary retention may be divided into 2 subgroups: l with normal sensory perception and 1 with reduced perception (526 ± 32 gm., p equals 1.6 x 10-9 ). Three patients with urinary urgency not associated with frequency did not perceive the urge to void until 541 ± 21 gm. (p equals 6.2 x 10-7 ) had been applied. Some elderly patients could not reproducibly report the urge to void. When lidocaine was applied topically within the bladder sensitivity was reduced by 210 ± 114 gm. (p equals 0.003). It is suggested that pressure sensitive receptors in the mucosa or submucosa of the bladder base and posterior urethra have a role in micturition, that their activity can be quantitated and that protocols designed to manage them may have impact on the care of patients with voiding disorders. For the bladder to function normally a series of integrated neuromuscular events that depend on intact motor and sensory components is required. 1 However, the diagnostic procedures available for the evaluation of abnormalities of vesical function emphasize almost exclusively the motor component, especially the detrusor muscle and urethral sphincter. 2 Sensory perception by the bladder and urethra largely has been neglected in the clinical investigation of bladder malfunction even though it has been suggested that abnormalities of bladder function may be owing to deficits of sensation. 3 Attempts to develop clinical tests of the sensory function of the bladder and urethra are almost as old as cystometry. Almost 100 years ago Genouville explored the relationship between bladder muscle sensation and bladder muscle contraction. The volume of fluid in the bladder and the desire to void were correlated.4 Rose noted ,Nhen the first desire to void was felt" and aithough he pv1tyu.«u•u~·"-' cystometry, quantitative study of the Nnaor,wuc:;;:·,-r,,.C,'r,·c·:;.+ of voiding did not proceed further. After his study cystometry focused on the motor components of bladder function, Current classifications of bladder malfunction are based upon detrusor and sphincter motor function. 6 The use of electrical stimulation for the quantitative evaluation of bladder sensibility reawakened interest in the sensory limb of bladder function. 7 Useful information has resulted from the study of faradic stimulation of bladder mucosa. 1 • 8 • 9 However, the technology is complex and invasive, and electrical current is not the natural stimulator of bladder nerves. As a result, electrical stimulation of the bladder has not been too helpful in clinical practice. A new technique has been developed to measure the amount of force that when delivered to the base of the bladder and posterior urethra just elicits an urge to void. This method is quantitative, reproducible, relatively noninvasive and inexpensive. With this technique a range of normal values of sensitivity was established and compared to the values found in groups of patients with various malfunctions of the lower urinary tract. Accepted for publication September 10, 1986. 245
Traction upon a balloon catheter must affect the bladder base, posterior urethra and, possibly, surrounding structures as well. Which of these areas is responsible for the sense of urge to void is unknown. Data in this study suggest that the cause may be mucosal sensors in the area of the trigone and bladder neck. On that basis and for simplicity the phenomenon is called trigonal sensitivity. METHODS
The technique for quantitative measurement of trigonal sensitivity is based upon the clinical observation that traction upon an indwelling balloon catheter causes an urge to void. A spring that is displaced 4 cm, by 550 gm. pressure was housed in a gauge that had a hook adapted to engage a Foley catheter (fig, 1). The balloon of the catheter was filled with 10 ml. water. Traction was applied at a rate of about 18 gm. per second until the patient noticed an urge to void. At that moment the amount of displacement of the spring was noted. Patients were not told
FIG. 1. Cutaway view of bladder with inflated Foley balloon pressing upon trigone. Gauge attaches directly to Foley catheter and is read directly.
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to expect an urge to void. They were asked if they experienced an urge to void at the beginning of the study before any traction was applied, and they were coached to notice any changes. Occasionally, 1 or 2 preliminary applications of traction were needed before the patient learned to respond appropriately. Each measurement was done in triplicate. If any 2 of the 3 recordings differed by more than 36 gm. the result was considered unreliable. Only 2 patients failed to meet the criteria for acceptance. When other urological tests were to be performed evaluation of pressure sensitivity was done first, followed by cystometry, urethral profilometry or cystoscopy. Fifty-eight male and female patients were evaluated. No difference in response was noted as a result of sex. All patients were fully alert during the examination and care was taken to ensure that narcotics, sedatives, and autonomic system agonists and antagonists were not being used at the time of the test. Nine patients had Foley catheters in place for purposes unrelated to micturitional disorders. These patients were normal with respect to function of the lower urinary tract and are considered as controls, leaving 49 patients available for study. Twelve other patients were studied before and after intervention: 7 before and after prostatectomy, and 5 before and after instillation of a topical anesthetic agent into the bladder. Statistical analyses were done by Student's t test for unpaired data. RESULTS
In normal patients trigonal sensitivity ranged from 162 to 340 gm., with an average of 245 ± 47 gm. (standard deviation) (fig. 2). Eight patients were studied after prostatectomy. Three days postoperatively, when analgesics were no longer being administered, the amount of traction required to elicit an urge to void was 344 ± 48 gm., which was significantly greater than that found among the normal patients (p = 0.0003). Of 11 patients with lower tract irritative symptoms, including urgency and frequency, 9 had prostatitis or cystitis, 1 had an infiltrating transitional cell carcinoma of the trigone and 1 had ureteral orifice trauma secondary to stone extraction by basket 2 days before the study. The force required to stimulate an urge to void in this group was 132 ± 50 gm., an average of 50 gm. below normal and highly statistically different from the normal group (p = 0.0003). Three men were studied at least 6 months after radical treatment for prostatic carcinoma: 2 with radical prostatectomy and 1 with radiation therapy. The force required to induce an urge to void in these patients was 469 ± 54 gm., each value being higher than that seen in any normal subject. This group differed significantly from normal (p = 0.0002). Three
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Two elderly patients (83 and 94 years old) were not able to report consistently the moment when the urge to void was noted. These were the only 2 patients whose variation in the 3 observations exceeded 36 gm. Trigonal sensitivity was measured before and 3 days after prostatectomy in 7 patients (fig. 3). The difference between the values was significant (p = 0.007). In 5 patients the operation was an initial prostatectomy. The results for each of these 5 patients were similar. In 2 patients (cases 1 and 2, fig. 3) the clinical situation was exceptional. Since the results of the test differed from the others these cases are reviewed. In patient 1 transurethral prostatectomy included only tissue from the apex of the prostate and no tissue was removed from the area of the bladder neck. Thus, the putative sensors would not have been altered. Patient 2 had undergone prostatectomy 8 years earlier and he returned with symptoms of urinary outflow obstruction. Recurrent prostatic tissue was resected and, presumably, the mucosa containing the sensors had been removed at the earlier prostatic resection. In 5 additional patients who complained of urinary urgency 600-
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women with urinary stress incontinence had values within the normal limits. There were 8 patients who presented with acute urinary retention: 5 after nonurological procedures and 3 had benign prostatic hyperplasia. The values in the latter group ranged widely and it was not possible to distinguish the values in these patients as a group from those in the normal group. The 11 patients with chronic urinary retention were divided into 2 subgroups: 1 with an average stimulation force of 526 ± 32 gm. and 1 with 280 ± 20 gm. The 8 patients with reduced sensitivity had spontaneous detrusor contraction associated with bladder distension. The remaining 3 patients with chronic urinary retention had normal trigonal sensitivity and total absence of detrusor contraction despite filling the bladder with more than 700 cc. One of these 3 patients had a form of hollow visceral myotonia10 and the cause of the atonia in the other 2 was not determined. Three elderly women noticed that periods of 3 to 4 hours could pass without the need to void but that when the urge occurred voiding was imperative and irresistible. The average force needed to stimulate an urge to void in these 3 patients was more than 550 gm. (the spring is compressed fully at 550 gm.) and the difference from normal was significant (p ~6 X
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FIG. 3. Trigonal sensitivity was measured before and 3 days after prostatectomy. With 2 exceptions all patients became less sensitive to trigonal pressure. Patient 1 had removal of apical prostatic tissue only, while bladder neck and most of posterior urethra were preserved. Patient 2 had had prostatectomy years earlier and returned with recurrent obstructive symptoms.
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and frequency the sensitivity was measured initially and after a topical anesthestic was given via the catheter. The differences between these 2 measurements were significant (p = 0.003) (fig. 4). DISCUSSION
When pressure is applied to the bladder neck and posterior urethral region normal people report an urge to void. In earlier studies of bladder sensitivity electrical current was used to stimulate the bladder and subjects reported a burning or tingling sensation.'· 8 ' 9 The difference in the subjective response suggests that the pressure technique may resemble more closely the natural physiological condition than the faradic techniques. Bladder sensitivity and, more specifically, trigonal and posterior urethral sensitivity have been largely ignored by bladder physiologists, probably for 2 reasons. 1) The design of the urodynamics laboratory favors recording either neural or muscular activity and not sensory responses. The urge to void that occurs during cystometry is not subject to quantification and, thus, it usually goes unnoted. 2) The end point of sensation, that is the feeling of an urge to void, is subjective and only observable through the use of language. The only appropriate subjects for investigation of this parameter are humans, so its place in the investigative urodynamics laboratory has been restricted. Physiological and morphological studies indicate that the bladder and urethra have proprioceptive and exteroceptive sensory innervation." Sensations evoked during bladder filling are proprioceptive in nature and are believed to be caused by stimulation of nerve endings in the muscle layers of the bladder.12 The motor response to proprioceptive receptor stimulation includes a low amplitude contraction of the detrusor muscle and relaxation of the smooth muscles of the proximal urethra. 11 Sensations evoked with touch and, most likely, modest amounts of pressure, such as were applied in this study, are exteroceptive and are believed to be caused by stimulation of nerve endings in the mucosa! layers of the bladder. 12 The pressure sensors probably are located in the mucosa, while other sensors are known to be located more deeply. 13 The ability of topical anesthetic agents to block pressure-induced urge to void supports the suggestion that the pressure receptors responsible for sensitivity are located in the mucosa. The fact that prostatectomy, an operation that alters the trigone but not the distal sphincter nor periprostatic structures, reduces sensitivity also supports the suggestion that sensitivity receptors are in the mucosa and not the prostatic capsule, other surrounding structures or the distal urethral sphincter. A study 3 days
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after prostatectomy may be difficult to interpret, for example it is not known if sensitivity to pressure returns much later after prostatectomy. Nonetheless, the suggestion that the receptors are located in the mucosa of the bladder neck and trigone seems to be strengthened by this observation. Patients with symptoms of lower urinary irritation had lower thresholds of sensory perception than normal subjects (p = 0.00003). This finding is in agreement with data obtained by mucosal electrosensitivity testing. 1 • 8 • 9 It cannot be determined from the data if the hypersensitivity is a primary condition or if it results from the pathological condition that causes the irritative symptoms. However, it seems clear that the irritative symptoms relate in a measurable way to the state of the trigonal sensing mechanism. This objective examination may find clinical use in distinguishing patients with various types of irritative syndromes, for example the urethral syndrome, urethritis and trigonitis. As a group, patients with acute urinary retention showed no specific pattern of trigonal sensitivity and values varied over the entire possible range. Bladder sensitivity seems to have little to do with acute retention but the size of the study does not permit a thorough examination of possible variables, such as the volume of retained urine or patient age. Further study will be required to address these possibilities. Chronic urinary retention seems to be associated with 2 distinct patterns of sensitivity: 1) reduced sensory perception and intact detrusor contractility (an average of 524 gm. pressure was required before the urge to void occurred) and 2) sensitivity within the normal range. Patients with the first pattern had recognizable disorders, for example multiple sclerosis, discogenie disease or local problems, such as a history of radiation therapy. Patients with the second pattern, that is normal trigonal sensitivity levels, had abnormalities of the detrusor muscle (familial hollow visceral myotonia and detrusor atony). Only 2 of the 58 patients (3.4 per cent) in this unselected series were unable to distinguish pressure stimulation with a reproducibility of 36 gm. or less. Both were elderly patients with incontinence but with normal cystometrograms. Urethral hyposensitivity has been noted previously in the elderly, 1 The inability to perceive trigonal sensation may be a factor contributing to incontinence in the elderly. Three patients with stress urinary incontinence had normal sensitivity. This finding is consistent with the hypothesis that stress urinary incontinence is owing to a loss of urethral and detrusor support structures rather than to sensory loss. The finding of normal trigonal pressure sensitivity may be important in confirming the diagnosis of stress incontinence. Three female patients demonstrated urgency incontinence without urinary frequency or dysuria. In each case trigonal sensitivity was decreased severely. A similar finding has been noted with urethral mucosa! electrical stimulation. 8 Trigonal sensors may function as an early warning signal during bladder filling. Disability of the pressure sensors may preclude an early sense to void in these patients with the result that severe urgency owing to detrusor distension appears as the first signal to void. The measurement of trigonal sensitivity by this method is simple and reproducible. Its use rnay improve understanding and management of disorders of bladder function.
100_ REFERENCES 1. Powell, P. H. and Feneley, R. C. L.: The role of urethral sensation
0-
in clinical urology. Brit. J. Urol., 52: 539, 1980. 2. Barrett, D. M. and Wein, A. J.: Controversies in Neuro-Urology.
147
±: 96
410±86
p:0.003
FIG. 4. Effect of topical anesthesia on trigonal sensitivity. Patients were given 15 cc 2 per cent lidocaine hydrochloride via Foley catheter after initial and second determinations were made. Most of patients in study were taken from group with irritative symptoms.
New York: Churchill Livingstone, chapt. 1-6, pp. 1-211, 1984. 3. Bradley, W. E., Timm, G. W. and Scott, F. B.: Cystometry. IL Central nervous system organization of detrusor reflex. Urology, 5: 578, 1975. 4. Genouville, F. L.: Du role de la contractilite vesicale dans la miction normale. Arch. de Physiol., 6: 323, 1894.
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KLEIN
5. Rose, D. K.: Cystometric bladder pressure determinations: their clinical importance. J. Ural., 17: 487, 1927. 6. Krane, R. J., Siroky, M. B. and Wein, A. J.: Classification of voiding dysfunction. In: Controversies in Neuro-Uralogy. Edited by S. M. Barrett and A. J. Wein. New York: Churchill Livingstone, chapt. 8,pp. 233-252, 1984. 7. Markland, C., Chou, S., Swaiman, K. F., Westgate, H. D. and Bradley, W. E.: Evaluation of neurologic urinary dysfunction. Surg. Forum, 16: 504, 1965. 8. Kiesswetter, H.: Mucosa! sensory threshold of urinary bladder and urethra measured electrically. Ural. Int., 32: 437, 1977.
9. Frimodt-Moller, C.: A new method for quantitative evaluation of bladder sensibility. Scand. J. Ural. Nephral., suppl. 15, 6: 135, 1972. 10. Stafford, S. J., Ulshen, M. H. and Mandell, J.: Familial visceral myopathy. J. Ural., 131: 978, 1984. 11. Bradley, W. E., Timm, G. W. and Scott, F. B.: Innervation of the detrusor muscle and urethra. Ural. Clin. N. Amer., 1: 3, 1974. 12. Bradley, W. E., Timm, G. W. and Scott, F. B.: Cystometry. V. Bladder sensation. Urology, 6: 654, 1975. 13. Fletcher, T. F. and Bradley, W. E.: Neuroanatomy of the bladderurethra. J. Ural., 119: 153, 1978.