Mechanisms of action of botulinum neurotoxins, beta3-adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders: ICI-RS 2011

Nerve Root Injections

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. [email protected]

Journal of Publication : Neurourol Urodyn

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22275187

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2021-05-10

I have known Dr Akmal and his team for the past 8 years, I have seen him and his team ON and OFF for issues regarding my neck, C4/5, C5/6 , C6/7. I first had 3 lots of injections into this area back at the start of things. This helped me for 3 years. Dr Akmal did not want to operate at the time due to my age still been under 40 then. After 3 years I had to see Dr Akmal and his team again. We tried the injection route again but after a few attempts we then had to make the call to cut. I had C5/6 and C6/7 +/- C4/5 anterior cervical decompression and fusion / disc replacement carried out. This was a success and I was out of the hospital within 3 days and recovery took place for the next few months. This year I was operated on the back of my neck for a posterior cervical foraminotomy on the left side at the C5/6 and C6/7 levels. We tried the injections last year but this did not help. Due to Covid to this should have been carried out last year. Dr Akmal explained the risks include nerve injury, dural tear and pain post-operatively but the procedure is fairly routine and the risks are relatively low. Surgery has now taken place back in February. I was released the same day later that evening and been back for my check ups and things are looking up. I am currently training for a half triathlon that I will take part in second week of July. I am doing anything from 120 km to 170 km a week on the bike and running now upto 10 km a day on my running days. I have not been able to swim yet due to pools been closed but I have no issues with movement in me neck. I am very happy I chose Dr Akmal from the start. I did seen two others before him, they were happy to just cut and not look at what was best for me. I also strongly believe the newer technology Dr Akmal uses has really helped me any my life style I lead with sports. I know I would not have had the same results if I did not take the route with Dr Akmal. I really can’t say much more but I am very happy I met Dr Akmal when I did, he has been great and so has his team. Patient Miles McWilliams 😊

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2021-04-14

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2021-04-07

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Mechanisms of action of botulinum neurotoxins, ?(3) -adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders | Myofascial pain