BOTULINUM TOXIN: WHY USE IT IN THE LOWER URINARY TRACT
Authors:
M. B. Chancellor; D. Pacík
Authors‘ workplace:
Urologická klinika FN Brno
; Department of Urology, William Beaumont Hospital, Royal Oak, MI, USA
Published in:
Urol List 2009; 7(2): 5-11
Overview
Botulinum neurotoxins are well known for their ability to potently and selectively disrupt and modulate neurotransmission. Only recently have urologists become interested in the potential use of botulinum neurotoxin (BoNT) in patients with detrusor overactivity and other urological disorders. We will review mechanisms by which BoNT modulates acetylcholine and other biochemical messengers at presynaptic nerve terminals in the detrusor smooth muscle and possibly the urothelium. We will also review what is known about potentially important non-cholinergic mechanisms modulating the function of detrusor smooth muscle and bladder afferent sensory processing.
BoNT has received regulatory approval for a number of conditions characterized by excessive and unwanted muscle contractility or tonus in striated muscle (e.g., cervical dystonia, blepharospasm, hemifacial spasm, and limb spasticity secondary to central nervous system injury) or overactive secretion (e.g. hyperhidrosis). More recently, researchers have discovered that BoNT is effective in conditions such as overactive bladder and esophageal spasm, suggesting that BoNT’s effects on neurotransmission in smooth muscle appear to be similar to those in striated muscle [55]. BoNT is currently undergoing regulatory evaluation for urological disorders in the United States and the European Union. However, as the uses of BoNT continue to expand, it is important to be familiar with the mechanism by which the toxin works and to investigate any differences that may exist when it is applied to different tissue types.
A step-wise mechanism of action for the botulinum toxins was first suggested by Simpson [56] and involves toxin binding to, and internalization within, the presynaptic membrane of cholinergic neurons, followed by translocation into the neuronal cytosol and then inhibition of acetylcholine (ACh) release. This review explores these processes with regard to BoNT, its structure and its effects on the function of the lower urinary tract.
KEY WORDS:
botulinum toxin, bladder, prostate, incontinence
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