Abstract
Botulinum toxin A (BTX-A) is a powerful neurotoxin with long-lasting activity that blocks muscle contractions. In addition to effects on neuromuscular junctions, BTX-A also plays a role in sensory feedback loops, suggesting the potentiality for pain relief. Although the only approved indications for BTX-A in the bladder are neurogenic detrusor overactivity and refractory overactive bladder, BTX-A injections to treat bladder pain refractory to conventional therapies are also recommended. The mechanism of BTX-A activity in bladder pain is complex, with several hypotheses proposed in recent studies. Here we comprehensively reviewed properties of BTX-A in peripheral afferent and efferent nerves, the inhibition of nociceptive neurotransmitter release, the reduction of stretch-related visceral pain, and its anti-inflammatory effects on the bladder urothelium. Studies have also revealed possible effects of BTX-A in the human brain. However, further basic and clinical studies are warranted to provide solid evidence-based support in using BTX-A to treat bladder pain.
Highlights
Botulinum toxin, one of the most powerful neurotoxins in nature, is produced by the anaerobic, Gram-positive organism, Clostridium botulinum
When botulinum toxin A (BTX-A) is pharmacologically activated, it is cleaved to a 100-kDa heavy chain and a 50-kDa light chain that are connected by a single disulfide bond as well as noncovalent bonds [1,6]
BTX-A binds to nerve terminals because of the high affinity of its heavy chain for synaptic vesicle-associated protein-2 (SV2) allowing the toxin to be endocytosed into synaptic vesicles [7]
Summary
One of the most powerful neurotoxins in nature, is produced by the anaerobic, Gram-positive organism, Clostridium botulinum. Of the seven distinct serotypes (A through G), botulinum toxin A (BTX-A) shows the longest duration of activity in blocking transmission at the neuromuscular junctions, making it the most popular form for clinical use. In 1988, Dykstra et al were the first to use BTX-A in a urological application by injecting it into the urethral sphincter to treat detrusor sphincter dyssynergia in spinal cord injury patients [2]. BTX-A injection has been widely used in lower urinary tract diseases and is approved for patients with both overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). In addition to OAB and NDO, using a BTX-A injection to treat the pain of interstitial cystitis/bladder pain syndrome (IC/BPS) is recommended in patients refractory to conventional therapies [3]. IC/BPS is Toxins 2020, 12, 98; doi:10.3390/toxins12020098 www.mdpi.com/journal/toxins
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