BACKGROUND: Botulinum neurotoxins type A (BoNT/A), beta(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. METHODS: 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 beta(3)-adrenergic receptors on dorsal root ganglion (DRG) neurons. RESULTS: Our unique approaches revealed the direct effects of BoNT/A in inhibiting neuropeptide release and firing rates in afferents following bladder injections. beta(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. DISCUSSION: The questions raised during the plenary session of the 2011 International Consultation on Incontinence-Research Society meeting regarding the benefits of BoNT/A, beta(3)-adrenergic receptor agonist and PDE5 inhibitor treatments of overactive bladder are addressed. CONCLUSION: 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
Keywords : Adrenergic beta-3 Receptor Agonists,agonists,Animals,Botulinum Toxins,Botulinum Toxins,Type A,Calcium Signaling,complications,Decerebrate State,Disease Models,Animal,Dose-Response Relationship,Drug,drug effects,drug therapy,etiology,Female,Immunohistochemistry,Injections,innervation,metabolism,methods,Mice,Neurons,Neurotoxins,pharmacology,Phosphodiesterase 5 Inhibitors,physiopathology,Sensory Receptor Cells,Spinal Cord,Spinal Cord Injuries,Universities,Urinary Bladder,Urinary Bladder,Neurogenic,Urinary Bladder,Overactive,, Action,Botulinum,Neurotoxins, back pain massage
Date of Publication : 2012 Mar
Authors : Kanai A;Zabbarova I;Oefelein M;Radziszewski P;Ikeda Y;Andersson KE;
Organisation : Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. ajk5@pitt.edu
Journal of Publication : Neurourol Urodyn
Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22275187
The London Spine Unit : Harley Street UK. Specialists in Cutting Edge Technologies for Spinal Surgery
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