Targets for botulinum toxin in the lower urinary tract

Abstract

There is now robust information to support that the mechanism of action of BoNT/A in the bladder involves neurotransmitter release from nerve fibers and urothelial cells. Which neurotransmitter is more relevant is, however, unclear. Likewise, the long duration of effect, the importance of the volume of vehicle injected and the selection of specific injection sites, like the trigone, needs further evaluation.

Current and potential urological applications of botulinum toxin A

“…17 For this reason, cleaved SNAP25 is considered an ideal marker of sites of BoNTA action and, there fore, an important target in future research. 17,18 Despite this apparent accumulation of BoNTA in parasympa thetic nerves, in 2014, the presence of binding protein SV2 as well as the target protein SNAP25 was demon strated within the bladder mucosa using immunohisto chemical staining and western blotting methods. 19,20 This finding indicates that the effects of BoNTA in the urinary bladder are more complex than previously thought, and intravesical delivery of BoNTA into the urothelium by might be both possible and clinically relevant.…”

“…18,21,22 Nowadays, the urothelium is proven to not only act as a barrier but also has important sensory signal ling functions. 23 BoNTA might also alter the release of ATP, neurotrophins and nitric oxide (NO) from the urothelium.…”

“…23 BoNTA might also alter the release of ATP, neurotrophins and nitric oxide (NO) from the urothelium. 18,24,25 Effects on muscle contraction In striated muscle, BoNTA temporarily blocks the release of acetylcholine at the neuromuscular junction, influencing both α motor neurons, which innervate extra fusal muscle fibres, and γ motor neurons, which inner vate intrafusal muscle fibres. 26 In the urinary bladder, the release of acetylcholine from both preganglionic and postganglionic parasympathetic nerves is blocked after BoNTA administration.…”

“…26 In the urinary bladder, the release of acetylcholine from both preganglionic and postganglionic parasympathetic nerves is blocked after BoNTA administration. 18,21 The effects of BoNTA on the sympathetic nervous system within the urinary bladder are less well established. 18 BoNTA administration and the resulting SNAP25 cleavage inhibits release of vesicu lar noradrenaline, thus inhibiting the activation of both αadrenoceptors and β 3 adrenoceptors, which mediate bladder neck contraction and detrusor relaxation, respec tively.…”

Advances in Diagnosis and Treatment of Interstitial Cystitis/Painful Bladder Syndrome

“…With strong analgesic properties impairing release of neurotransmitters from nociceptive neurons both at their peripheral and spinal cord endings [94,95], OnabotA injection in the bladder wall has been shown to decrease bladder pain and ameliorate nocturia and frequency in IC/BPS patients refractory to standard treatment [36,96]. Additionally, recent evidence has shown that the analgesic effect after repeated injections of OnabotA is superior to a single injection [97,98].…”