Incontinence Research Society Research Articles

Mechanisms of action of botulinum neurotoxins, β3‐adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders: ICI‐RS 2011

Botulinum neurotoxins type A (BoNT/A), β(3)-adrenergic receptor agonists, and phosphodiesterase type 5 (PDE5) inhibitors are promising agents that mitigate lower urinary tract symptoms by attenuating the sensory system. However, whether they act directly on afferent nerves or indirectly through the other cell types is unclear. Spinal cord transected female mice were used as a model for neurogenic bladder overactivity. In vivo methods utilized decerebrate mouse cystometry. In vitro approaches included optical mapping of Ca(2+) transient, single unit afferent nerve recordings and tension measurements from bladder sheets and wall cross-sections. Immunohistochemistry was used to measure the expression of β(3)-adrenergic receptors on dorsal root ganglion (DRG) neurons. Our unique approaches revealed the direct effects of BoNT/A in inhibiting neuropeptide release and firing rates in afferents following bladder injections. β(3)-adrenergic receptor agonists are demonstrated to directly inhibit afferent nerve firing independent of the relaxing effects on bladder smooth muscle. Moreover, data suggest the expression of these receptors on DRG neurons that send projections to the bladder. The mechanism of action of PDE5 inhibitors on bladder overactivity is discussed. The questions raised during the plenary session of the 2011 International Consultation on Incontinence-Research Society meeting regarding the benefits of BoNT/A, β(3)-adrenergic receptor agonist and PDE5 inhibitor treatments of overactive bladder are addressed. Our findings suggest that the abovementioned agents, in low enough concentrations, can directly inhibit afferent excitability without decreasing detrusor contractility. Accordingly, they have considerable potential for treating the sensory component of lower urinary tract dysfunctions.

The 2nd international consultation on incontinence, research society (ICI‐RS) Meeting 2010

The 2nd international consultation on incontinence, research society (ICI‐RS) Meeting 2010

Researching bladder afferents—determining the effects of β3‐adrenergic receptor agonists and botulinum toxin type‐A

A substantial portion of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated, enhanced and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source for drug targets. Established drug therapies such as muscarinic receptor antagonists, and two emerging therapies, β(3) -adrenergic receptor agonists and botulinum toxin type-A, may act partly through afferent mechanisms. This review focuses on these two new principles and new and established methods for determining their sites of action. It also provides brief information on the innervation of the bladder, afferent receptors and transmitters and how these may communicate with the urothelium, interstitial cells and detrusor smooth muscle to regulate micturition. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms and urgency sensations are also covered. This work is the result from 'Think Tank' presentations, and the lengthy discussions that followed, at the 2010 International Consultation on Incontinence Research Society meeting in Bristol, UK.

Nocturia: New Directions

The Nocturia Think Tank (TT) met during the 2010 meeting of the International Consultation on Incontinence-Research Society to discuss present knowledge and future directions in care and research of this prominent component of the spectrum of lower urinary tract symptoms. Questions raised included whether nocturia should be re-defined as a function of its bother, effects on quality of life, and economic impact upon society. At issue is the need to delineate the determinants of successful nocturia management. The multifactorial nature of nocturia requires that progress in its treatment will be dependent upon the cooperative investigation on the part of urologists, urogynecologists, geriatricians, epidemiologists, medical economists and pharma. Areas for future avenues of research were outlined at the conclusion of the meeting.

The international consultation on incontinence, research society (ICI‐RS)

Neurourology and UrodynamicsVolume 29, Issue 4 p. 596-597 Review Article The international consultation on incontinence, research society (ICI-RS)†‡ Paul Abrams, Corresponding Author Paul Abrams [email protected] [email protected] Bristol Urological Institute, Southmead Hospital, Bristol, UKBristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UK.Search for more papers by this authorLinda Cardozo, Linda Cardozo King's College Hospital, London, UK Professor of Urogynaecology.Search for more papers by this authorAlan Wein, Alan Wein Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Professor of Urology.Search for more papers by this author Paul Abrams, Corresponding Author Paul Abrams [email protected] [email protected] Bristol Urological Institute, Southmead Hospital, Bristol, UKBristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UK.Search for more papers by this authorLinda Cardozo, Linda Cardozo King's College Hospital, London, UK Professor of Urogynaecology.Search for more papers by this authorAlan Wein, Alan Wein Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Professor of Urology.Search for more papers by this author First published: 22 April 2010 https://doi.org/10.1002/nau.20920Citations: 11 † Conflict of Interest: none ‡ Christopher Chapple led the review process. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume29, Issue4April 2010Pages 596-597 RelatedInformation

Post‐prostatectomy stress urinary incontinence: What treatment for which patient?

Editorial Comment: This is a summary article written by the “committee” assigned to consider this problem at the International Consultation on Incontinence-Research Society meeting held in June 2009. The overall conclusion is that it is not possible at this time to answer which treatment is suitable for which patient; this will require good quality research with adequate followup duration, consistent definition, and standardized tools for pre-management and post-management evaluations. The following topics are discussed: 1) prediction (the degree of pelvic floor development is related to the recovery of continence 3 months after surgery but data further on are lacking); 2) protective or rehabilitative effect of pelvic floor muscle exercises (“relatively weak evidence based as to efficacy and how best to deliver such training”); 3) pharmacological management (expectation that to be effective, some urethral sphincter activity must remain; “well conducted, multicenter, [randomized controlled trials] with long-term followup would be needed to adequately judge duloxetine treatment but there is no agreement whether such trials are warranted”); 4) bulking agents (“Although the procedure seems to be easy to perform and patients are initially satisfied, results are of short durability. The present evidence does not appear to warrant additional research, and the overall strategy of bulking agents may have limited scope in [post-prostatectomy incontinence]”); 5) adjustable compressive balloon therapy (current case series report high initial improvement levels with high necessity of volume readjustment; “additional [randomized controlled trials] comparing adjustable balloons to [artificial urinary sphincter] with long-term followup would be beneficial”); 6) slings and tapes, both nonadjustable and adjustable (relatively high “success”—dry or improved—rates reported with series followed 2 to 4 years); 7) artificial urinary sphincter (relatively high success rate, longest followup; current reports cited which predict superior efficacy in men with higher incontinence grades but “the efficacy of the [artificial urinary sphincter] is partly counteracted by purchase price, operation time, and surgical or mechanical complications. Consequently there is an increasing tendency towards treating lower incontinence grades with alternative techniques, but only time will tell whether this is beneficial to the treated patients”).