Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity.
BACKGROUND
Treatment of human bladder overactivity with intradetrusor Botulinum-A neurotoxin (BoNT/A) injections temporarily blocks the presynaptic release of acetylcholine from the parasympathetic innervation and produces a paralysis of the detrusor smooth muscle. The efficacy of the treatment exceeds that expected from simple detrusor muscle paralysis, however, and its effect of reducing urgency is greatly welcomed by patients.


OBJECTIVE
To examine whether BoNT/A has a complex effect on sensory mechanisms by inhibiting vesicular release of multiple excitatory neurotransmitters by urothelial and suburothelial nerves and reducing axonal expression of SNARE-complex dependent proteins.


METHODS
A literature review.


CONCLUSIONS
We propose that a primary peripheral effect of BoNT/A is the inhibition of release of acetylcholine, ATP, substance P, and reduction in the axonal expression of the capsaicin and purinergic receptors. This may be followed by central desensitization through a decrease in central uptake of substance P and neurotrophic factors. The summation of these effects is a profound and long-lasting inhibition of those afferent and efferent mechanisms that are thought to be the pathophysiological basis for DO.
Apostolidis
Apostolos
A
Department of Uro-Neurology, the National Hospital for Neurology and Neurosurgery, London, UK.
Dasgupta
Prokar
P
Fowler
Clare J
CJ
D000109:Acetylcholine / Q000378:metabolism; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A; D000109:Acetylcholine