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Keywords:

  • bladder muscle;
  • smooth;
  • urodynamics;
  • micromotion

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

OBJECTIVE

To describe an observational study to establish whether localized activity arises in the normal human bladder, and whether there is any correspondence between changes in such activity and reported sensation.

PATIENTS, SUBJECTS AND METHODS

The generation of sensory information by the bladder depends on afferent stimulation by increased tension within the bladder wall. Autonomous bladder activity is apparent in several species, which is often localized and multifocal, giving rise to localized areas of stretch. Thus afferent activity may partly result from localized distortions of the bladder wall. Fourteen women patients presenting with increased bladder sensation during filling-phase cystometry were compared with six asymptomatic women volunteers. Localized bladder activity was assessed by the micromotion detection (MMD) method, using eight electrodes mounted on a Silastic balloon; local displacements of the electrodes were recorded as changes in electrical resistance, which were used to compute changes in the distance between each pair of electrodes.

RESULTS

In two of the six volunteers, micromotions were seen in the extraperitoneal (ventral) portion of the bladder. Women with increased sensation on filling cystometry had a significantly higher prevalence of localized activity than the control group during MMD recording. The localized activity was more sustained and at a higher frequency than in asymptomatic women. All nine women reporting urinary urgency during MMD recording had localized contractile activity, while only four had phasic increases in detrusor pressure during the episodes of urgency.

CONCLUSIONS

By measuring localized contractions within the bladder wall, we established a significant difference in the prevalence of localized activity between the groups studied, but there was no objective difference with conventional urodynamic studies. There was also a difference in the character of the localized contractions, with the exaggerated activity in the symptomatic group corresponding with the reported sensations. These findings suggest that localized distortion of the bladder wall stimulates afferent activity, and that the human detrusor may be functionally modular


Abbreviations
(MM)D

(micromotion) detection.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The micturition reflex is controlled by the pontine micturition centre, which integrates afferent information from the lower urinary tract and other sites to determine the transition from the urine storage phase to voiding. At a certain level of afferent activity, this transition is more or less inevitable, setting an upper limit to the volume of urine that the bladder can hold in the intact animal. The physiological basis of the generation of sensory information by the bladder depends on the stimulation of afferent fibres as a consequence of increased tension within the bladder wall. The most sensitive afferents are ‘in-series tension receptors’, activated by increase in volume and by detrusor contraction; these low-threshold afferents have endings located in the detrusor smooth muscle and mostly have small myelinated axons (A-δ) [1].

The bladders from adult animals of several species show complex autonomous activity when freed of central nervous input [2–6]. At baseline this activity is localized and can be multifocal, with separate areas of the bladder wall (‘modules’[7]) contracting independently [3]. Established autonomous bladder activity reveals the presence of coupling, in which the activity in separate modules shows a constant phase relationship [2], or a phase cycling gradually passing from in-phase to antiphase and back again [8]. In response to an increase in intravesical volume, or stimulation by applying a muscarinic agonist at low concentration, propagating contraction waves emerge [5]. Localized areas of stretch can be detected during both multifocal and propagating autonomous bladder activity [2,3,5]. This has implications for the generation of afferent activity from the bladder wall [2], as it is likely that localized stretch will stimulate the in-series tension receptors. Thus afferent activity may represent not just a graded response to uniform distension of the bladder by the increasing urine volume during filling, but an additional component representing the sum of the localized distortions within the bladder wall resulting from its modular structure [9]. Such localized activity, described as ‘micromotions’ (MMs) appear to contribute to symptoms of chronic pelvic pain syndrome [10]. In this report, we describe observational studies to establish whether localized activity is a feature of the normal human bladder, and whether there is any correspondence between changes in such activity and reported sensation.

PATIENTS, SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The study group was drawn from women patients presenting with increased bladder sensation during filling-phase cystometry, defined as an early first sensation of bladder filling and/or an early strong desire to void, at low bladder volume, and which persists [11]. Control subjects were asymptomatic women volunteers, with no known urological complaint. Study subjects underwent filling and voiding urodynamic studies and urine microscopy. Exclusion criteria were: detrusor overactivity, use of anticholinergic drugs (including antidepressants), lower urinary tract malignancy, active lower UTI, pelvic endometriosis or chronic pelvic pain syndrome.

Localized activity in the bladder wall was assessed by the MM detection (MMD) method [10], which uses eight electrode disks mounted on the inner surface of a high-compliance Silastic balloon, protruding 2 mm from the outer surface of the balloon. The disks are mounted equatorially on the balloon in a plane at ≈ 60° to the plane of the catheter on which the balloon is mounted (Fig. 1). From each electrode, a fine insulated wire is passed through the catheter lumen. Electrode voltages were amplified, digitized and recorded. Local displacements of the electrodes are recorded as changes in electrical resistance between neighbouring electrodes. Changes in the distance between two electrodes are registered as changes in the voltage while the encompassing electrodes are injecting current. As the voltage difference between neighbouring electrodes is proportional to resistance, which depends on distance, the spacing of eight equatorial segments could be derived as described previously [10]. A separate lumen is used for intravesical pressure recording and to vary the volume of the balloon. A 6 F catheter placed alongside the MMD catheter ensured a constant total intravesical volume, by removing the subject's urine output during the recording. Simultaneously, intra-abdominal pressure was recorded with a rectal catheter. After the patient was asked to void, the MMD catheter was passed and filled to 200 mL. MMD was recorded over a 30-min period. Study subjects were categorized according to the MMD findings into the following groups; MMs absent (MM–) or present (MM+), phasic detrusor activity absent (pdet–) or present (pdet+), subjective report of urinary urgency absent (urge–) or present (urge+). Groups were compared statistically using the two-tailed Student's t-test. The study was approved by the Research Ethics Committee of the University Hospital of Rotterdam. Informed consent was obtained from each subject.

image

Figure 1. Schematic illustration of the MMD catheter, showing the location of the recording electrodes in a circle offset from the axis of the catheter on which the balloon was mounted. One catheter lumen was used for balloon filling and pressure measurement; a separate channel carried the wires for the electrodes.

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RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Six asymptomatic controls were compared with 14 patients with increased bladder sensation on filling cystometry, but with no detrusor overactivity. The median (range) age was 48 (35–67) years, with no significant difference between the groups. During insertion of the catheter many of the women reported discomfort as the balloon passed through the urethra, although this usually settled quickly once the balloon was in place.

In two of the six asymptomatic volunteers, MMs were detected in the extraperitoneal (ventral) portion of the bladder (Table 1). The MMs were characterized by gradual onset and decline, occurring at a frequency of about one contraction/min (Fig. 2). These MMs were not associated with any change in intravesical pressure or subjective report of sensation of urinary urgency (Table 1). In addition, some of the traces showed variation in electrode separation coincident with the respiratory cycle. This was seen in dorsal electrodes, which are more likely to be applied to that part of the bladder whose serosal aspect is intraperitoneal. We therefore presume these movements detected by the MMD recording were a result of excursion of the diaphragm and abdominal musculature.

Table 1.  Prevalence of MM activity and phasic increases in detrusor pressure detected during MMD recording, and the correspondence with reported sensation of urinary urgency
ResultIncreased sensationControlP
MM+, pdet 6/142/60.36
urge+ 5/60/20.03
urge− 1/62/20.03
MM+, pdet+ 6/140
urge+ 4/60
urge− 2/60
MM−, pdet+ 00
MM−, pdet 2/144/60.02
image

Figure 2. MMD recording from a 46-year-old asymptomatic female volunteer. Intraluminal pressure in the balloon is plotted underneath, showing small pressure fluctuations caused by respiration; simultaneously measured abdominal pressure was identical to the intravesical pressure (not shown). The movement plots above (d1–d8) indicate electrode separation on the balloon; d1–d4 were located ventrally (corresponding to the extraperitoneal part of the bladder), while d5–d8 recorded from the dorsal (intraperitoneal) region. The figure appears complex, but only two different types of activity are present. Dorsal electrodes, especially d7 and d8, showed variations in length synchronous with abdominal pressure fluctuations, consistent with the intraperitoneal location of this part of the bladder. Different activity was apparent in d3 and d4, from electrodes located in relation to the extraperitoneal part of the bladder. These showed reciprocal changes in length, i.e. elongation of one occurred during contraction of the other. This activity arose independently of the variation in pressure, at a frequency of about one contraction every minute, rising and falling gradually. During recording, the subject reported no sensations of urgency.

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Women with increased sensation on filling cystometry had a significantly higher prevalence of MM activity than the control group (12/14, as opposed to 2/6 control, P = 0.02). The MM activity differed from that in asymptomatic individuals, in that it was more sustained and occurred at a higher frequency (2–5 contractions/min; Fig. 3). All nine women reporting urinary urgency during MMD recording were in this group. All were found to have MM activity during the episodes of urgency (Table 1), while only four had phasic increases in detrusor pressure during the episodes of urgency (MM+, pdet+). The urgency symptoms thus appeared to correspond more closely to MM activity than to phasic increases in intravesical pressure.

image

Figure 3. MMD recording from a 55-year-old women with increased bladder sensation on filling cystometry. During the time of recording shown the patient reported two episodes of urinary urgency, as indicated by the bars above the traces. At the same time there was obvious localized activity, with reciprocal length changes apparent in traces d2 to d7, most marked in d3 and d4. Close examination shows further episodes of low-amplitude reciprocal activity not associated with urgency, occurring every ≈ 20 s. Intraluminal pressure in the balloon is plotted underneath, with no overt change in pressure attributable to the localized contractions. The cause of the low-amplitude pressure fluctuations is unknown, but did not coincide with the respiratory cycle.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The basis of increased bladder sensation in the absence of unstable detrusor activity during filling cystometry (‘sensory urgency’) is little understood, yet it is highly prevalent and can be responsible for considerable morbidity. By measuring localized contractions within the bladder wall, we established an objective difference between the groups assessed, which was not apparent with conventional urodynamic studies; there was a significant difference in the prevalence of MM activity. There was also an apparent difference in the character of the MMs, the exaggerated MMs in the symptomatic group corresponding with the reported sensations. The main method available to assess bladder function clinically is conventional urodynamics, measuring pressure and flow during filling and voiding. However, we previously established that it is not possible to deduce the contractile activity within the bladder wall solely from the intravesical pressure trace [4,10]. The MMD method aims to address this deficiency, but detecting low-amplitude, localized contractions in the human is a substantial technical challenge in practice. Thus, that localized activity was detected in just two of the asymptomatic women could indicate either that only a subgroup of women manifest localized activity, or that the experimental approach was insufficiently sensitive.

The present results have a possible bearing on lower urinary tract pathophysiology. First, there are implications for generating sensory information by the bladder. Functionally, a large proportion of bladder afferents behave as ‘in-series’ tension receptors, responding both to distension and contraction [1,12], with many of the small myelinated afferents behaving as low-threshold mechanoreceptors [12]. They constitute the most sensitive distension receptors; they are probably responsible for the sensation of fullness and mediate the spinobulbospinal micturition reflex. It is easy to envisage these afferents being stimulated by localized distortions of the bladder wall. Thus, exaggerated localized contractile activity could in theory stretch adjacent non-contracting parts of the bladder wall, leading to enhanced sensory return, which would precipitate a feeling of urgency [2]. The observation of a group of women in whom local bladder contraction and strong urgency arose with no change in intravesical pressure suggests that pressure alone is not the main determinant of afferent activity. This supposition is supported by the finding that local tension within the cat bladder shows a closer correspondence with afferent activity than does intravesical pressure [13]. Thus, tension within the localized field supplied by an afferent fibre shows a closer relationship with mechanoreceptor activity than with intravesical pressure. Second, the present results suggest that the human detrusor may be functionally modular [7], as activity in an individual module would be seen as a regionally confined contraction, other parts of the bladder remaining unchanged in length, or elongating. Displacements occurring between neighbouring electrodes inevitably influence other nearby electrodes. Thus a local contraction will show as a shortening between one electrode pair, which would most likely increase separation in the electrode pairs flanking the contraction. Nonetheless, it is quite clear that such a pattern will not arise during a generalized isotropic and isovolumetric bladder contraction, which would cause no shortening of any of the electrode pairs, and would lead to a rise in intravesical pressure. Thus, the findings support the presence of localized contractions in the human bladder wall, which are clearly present in women with sensory urgency, and may be present in a proportion of asymptomatic women. Such activity appeared to be present in some asymptomatic women; in women with urgency, modular activity became exaggerated, coincident with the symptom.

The presence of the Silastic balloon may influence the behaviour of the bladder; this may explain the observation of phasic increases in detrusor pressure in women who had no detrusor overactivity on conventional filling cystometry. Phasic pressure activity could arise as a consequence of the Silastic balloon altering the compliance characteristics of the bladder; normally localized stretch might counteract the pressure effects of local contractions elsewhere by ‘damping’ the force generated by the contractions. This damping effect might be lost if the Silastic balloon of the MMD apparatus reduced the compliance of the lower urinary tract. Thus, detrusor overactivity and increased bladder sensation may have a common basis, which may explain why anticholinergic therapy can be effective in managing both groups.

In conclusion, increased bladder sensation is associated with localized contractile activity in the bladder wall, which is significantly more prevalent than in asymptomatic volunteers. The presence of low-amplitude localized contraction in control subjects suggests that the human bladder may be functionally modular.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The study was supported by charitable funds of the Newcastle University Hospitals Special Trustees. We are grateful to Prof Dr T.J.M. Helmerhorst, Head of the Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, in whose department the clinical data was collected.

CONFLICT OF INTEREST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

None declared. Source of funding: Newcastle University Hospitals Special Trustees.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES