Gommert van Koeveringe

On the origins of the sensory output from the bladder: the concept of afferent noise

For many people a recurrent strong desire to void, sometimes with incontinence, diminishes their quality of life. At present there are few insights into what underlies these problems. The condition is described as the ‘overactive bladder symptom complex’ but this definition is proving to be unhelpful. It focuses on overt bladder contractions rather than the main problem, which is altered and heightened sensation. Also, current approaches that describe bladder sensations as episodic and leading to voiding as ‘first and second sensation to void’ might also be misleading if they are taken too literally and used to suggest mechanisms. Current research is beginning to focus on the mechanisms that generate afferent information from the bladder and how it can become altered. As these views develop it is crucial that we appreciate the diversity of the bladder afferent system and distinguish between afferent and sensory information; in this review we explore this underlying complexity. The central nervous system (CNS) receives vast amounts of information from the bladder, which arises from different locations, uses different fibre types and involves different methods. The CNS is continually being bombarded with ‘afferent noise’. The challenge now is to understand the nature and components of this ‘afferent noise’ and which components are essential to sensation. The emerging picture is complex, but this complexity must not be negated or oversimplified. It must be embraced and incorporated it into thinking when designing experiments, analysing data, diagnosing patients and evaluating treatment.

The Underactive Bladder: A New Clinical Concept?

UNLABELLED Detrusor underactivity (DU) is an increasingly recognised cause of lower urinary tract symptoms in both men and women. There has been a lack of research into all aspects of this dysfunction, and as yet, no effective treatments exist. DU can be diagnosed at present only on the basis of an invasive urodynamic study. An international consensus group met at the International Consultation on Incontinence-Research Society and International Continence Society annual meetings in 2014 to consider the feasibility of developing a working definition of a symptom complex associated with DU. Drawing an analogy to detrusor overactivity (urodynamic diagnosis) and overactive bladder (symptom complex), the aim of this process is to help identify affected patients and facilitate further clinical and epidemiological research. PATIENT SUMMARY Bladder underactivity is an underresearched but important cause of urinary symptoms in men and women. In this paper, an international expert group presents a working definition for the symptoms that characterise bladder underactivity, with the aim of facilitating further research in this area.

The effects of exogenous prostaglandins and the identification of constitutive cyclooxygenase I and II immunoreactivity in the normal guinea pig bladder

To establish the functional consequences of exposing the isolated whole bladder preparation to exogenous prostaglandins (PGE1, PGE2, PGF2α) and to determine which cells express cyclooxygenase (COX) types I and II, to generate PG to effect these changes in vivo.

Prostaglandin Receptor EP1 and EP2 Site in Guinea Pig Bladder Urothelium and Lamina Propria

PURPOSE Urothelium has 2 main functions. It is a barrier to urine and has a sensory role. In response to stretch urothelium releases various substances that modulate afferent nerve activity. Recent data on the localization of cyclooxygenase type 1, the enzyme responsible for prostaglandin production, suggests that prostaglandin may have complex local action. MATERIALS AND METHODS The bladders of 7 guinea pigs were stained for prostaglandin receptors type 1 and 2, and costained for vimentin and cyclooxygenase I. RESULTS Prostaglandin receptor type 1 staining was seen in urothelial cells and in the suburothelium. Urothelial staining, which was often punctuate and weak, was detected in all urothelial cell layers, including suburothelial cells. In contrast, strong prostaglandin receptor type 2 staining was seen in the urothelium and in suburothelial cells. Cyclooxygenase I was absent in interstitial cells and umbrella cells with the highest concentration in the basal cell layer. CONCLUSIONS Interstitial cells express prostaglandin receptor types 1 and 2, indicating that they can respond to prostaglandin. Umbrella cells do not express cyclooxygenase I. Cyclooxygenase I was present in basal urothelial cells, making them a possible site of prostaglandin synthesis. Thus, prostaglandin produced by urothelium may target prostaglandin receptor types 1 and 2 in the urothelium and suburothelium. Therefore prostaglandin is hypothesized to have a role in signal regulation in the bladder wall.

Affective symptoms and the overactive bladder - A systematic review

BACKGROUND Overactive bladder syndrome (OAB) is characterised by urgency symptoms, with or without urgency incontinence, usually with frequency and nocturia. Although literature suggest an association between OAB, depression and anxiety, no systematic review has been presented. OBJECTIVE Systematically review the literature on the association of affective conditions with OAB. METHODS Systematic review according to the PRISMA guidelines. This review is registered in the PROSPERO register (CRD4201400664). RESULTS Forty-three articles were included, describing more than 80,000 subjects. Depression and OAB were positively associated in 26 studies, anxiety and OAB in 6 studies. Longitudinal studies reported: a) OAB subjects who developed depression/anxiety or b) depressed/anxious subjects developing OAB, or c) both. The quality of evidence in studies reporting an association between the co-occurrence of OAB and depression was rated level 3 in accordance with the GRADE framework. Evidence reporting on the co-occurrence of anxiety and OAB was rated GRADE level 2. Longitudinal associations between new onset of OAB in depressive subjects was GRADE level 2. Evidence reporting association of OAB with anxiety in longitudinal studies was of GRADE level 1. CONCLUSION To our knowledge, this systematic review is the first to give a comprehensive qualitative overview on the association between OAB and affective symptoms. Many evaluated studies failed to note longitudinal changes and lacked evidence of causality. Still, results revealed an association between OAB and affective symptoms and there is evidence for new onset of OAB in depressive subjects, but further research is necessary to examine the strength of the effect.

The additional value of ambulatory urodynamic measurements compared with conventional urodynamic measurements

Study Type – Diagnostic (exploratory cohort)

The role of prostanoids in urinary bladder physiology

Five primary prostanoids are synthesized by the cyclooxygenase enzymes, COX-1 and COX-2: the prostaglandins PGE2, PGF2α, PGI2, PGD2 and thromboxane A2. High levels of these signaling molecules have been implicated—in both animal models and human studies—in decreased functional bladder capacity and micturition volume and increased voiding contraction amplitude. Thus, inhibition of prostanoid production or the use of prostanoid receptor antagonists, might be a rational way to treat patients with detrusor muscle overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity. Although some promising results have been reported, the adverse effects of nonselective cyclooxygenase inhibitors are a major concern that restricts their use in the treatment of functional bladder disorders. Further preclinical and clinical studies are needed before cyclooxygenase inhibitors, prostanoid receptor agonists and antagonists become worthwhile therapeutic tools in this setting.

Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra.

To identify and characterize possible structural specialisations in the wall of the lower urinary tract (LUT) in the region of the bladder urethral junction (BUJ), with the specific objective of identifying regional variations in sensory nerve fibres and interstitial cells (ICs).

Detrusor underactivity: Pathophysiological considerations, models and proposals for future research. ICI-RS 2013

Detrusor underactivity, resulting in either prolonged or inefficient voiding, is a common clinical problem for which treatment options are currently limited. The aim of this report is to summarize current understanding of the clinical observation and its underlying pathophysiological entities.

Functional Detrusor Myoplasty for Bladder Acontractility: Long-Term Results

PURPOSE We present the long-term results of a multicenter investigation with latissimus dorsi detrusor myoplasty in patients with bladder acontractility caused by lower motor neuron lesion in whom there is no treatment alternative other than lifelong clean intermittent catheterization. MATERIALS AND METHODS From 2001 to 2008, 24 patients (median age 39 years, range 13 to 63, 16 males, 8 females) requiring complete clean intermittent catheterization 4 to 7 times daily underwent latissimus dorsi detrusor myoplasty at 4 centers worldwide. Before the procedure patients were on clean intermittent catheterization for a median of 55 months (range 17 to 195). Median followup was 46 months (range 8 to 89) and was performed by urodynamics and measurement of post-void residual urine volume. Bladder contractility index was calculated. The t test was used for statistical analysis. RESULTS Of the 24 patients 17 (71%) gained complete spontaneous voiding with a mean post-void residual urine volume of 25 ml (range 0 to 100). Mean bladder contractility index increased from 20.1 ± 7.6 to 176.2 ± 25.4 (p <0.001). In 3 patients (13%) the frequency of clean intermittent catheterization was reduced to 2 to 4 times daily with a mean post-void residual urine volume of 200 ml (range 150 to 250). Mean bladder contractility index was 12.0 ± 7.2 preoperatively and 68.7 ± 28.1 postoperatively (p = 0.12). Recurrent urinary tract infections (defined as the presence of clinical symptoms such as dysuria and fever, and microbiological evidence of germs) ceased in 21 of 23 patients (91%, mean preoperatively 8 per year). Four patients (17%) required clean intermittent catheterization with the same frequency as before the procedure (mean bladder contractility index preoperatively 22.5 ± 10.3 and postoperatively 26.0 ± 12.3, p = 0.83). No chronic pain at the donor site or vesicoureteral reflux was observed in any patient. CONCLUSIONS The results of this multicenter analysis demonstrate that latissimus dorsi detrusor myoplasty is an effective alternative to clean intermittent catheterization in a select group of patients with neurogenic bladder acontractility.