Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats

We investigated the effects of intrathecal application of GABAA- or GABAB-receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 wk after Th9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABAA and GABAB agonists (muscimol and baclofen, respectively) or GABAA and GABAB antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. In spinal-intact rats, the effects of bicuculline and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions were observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal-intact rats, intrathecal application of bicuculline induced DSD-like changes. These results indicate that GABAA- and GABAB-receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABAA receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible, at least in part, for the development of DSD after SCT.     

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.     

Absolute versus per unit body length speed of prey as an estimator of vulnerability to predation

To study whether absolute (m/s) or relative (body lengths/s) speed should be used to compare the vulnerability of differently sized animals, we developed a simple computer simulation. Human 'predators' were asked to 'catch' (mouse-click) prey of different sizes, moving at different speeds across a computer screen. Using the simulation, a prey's chances of escaping predation depended on its speed (faster prey were more difficult to catch than slower prey of the same body size), but also on its size (larger prey were easier to catch than smaller prey at the same speed). Catching time, the time needed to catch a prey, also depended on both prey speed and prey size. Relative prey speed (body lengths/s or body surface/s) was a better predictor of catching time than was absolute prey speed (m/s). Our experiment demonstrates that, in contrast to earlier assertions, per unit body length speed of prey may be more 'ecologically relevant' than absolute speed. Copyright 1998 The Association for the Study of Animal Behaviour.     

Botulinum toxin: poisoning the spastic bladder and urethra

Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine.     

Differential diagnosis and treatment of impaired bladder emptying

Although much attention is paid to urinary incontinence, the condition of incomplete bladder emptying is becoming more common with the aging of the US population and the widespread use of anticholinergic drugs to treat overactive bladder. This disorder can often be silent until end-stage presentation of overflow incontinence. In this article, we review the pathophysiologic conditions of the bladder and urethra that can cause impaired bladder emptying and discuss how to evaluate and screen the patient with a bladder that does not empty. In addition, we provide an overview of treatment options available for impaired bladder emptying and consider the research that is under way to find the best therapies for the failing bladder.     

Advances in the understanding of sress urinary incontinence and the promise of stem-cell therapy

The middle urethra and external urethral sphincter are the focus in management of stress urinary incontinence, and recent cellular-therapy research suggests a new paradigm in treatment. Cell-based therapies are most often described as using autologous multipotent stem cells procured from bone marrow in procedures that may be painful, require anesthesia, and yield low numbers of mesenchymal stem cells upon processing. In contrast, muscleand adipose-derived stem cells can be obtained easily in large quantities under local anesthesia. Instead of lifting the urethra with a sling or bulking up the urethral sphincter with collagen, we now have the potential to restore function with the use of autologous stem cells.