Understanding the Role of Botulinum Toxin A in the Treatment of the Overactive Bladder—More than Just Muscle Relaxation

The established use of botulinum neurotoxin type A (BoNT/A) therapy has been based on its reversible inhibition of acetylcholine (ACh) and associated muscle relaxation. Greater understanding of the pathophysiology of detrusor overactivity (DO), as well as macromolecular analysis and analysis of the duration of the effects of BoNT/A treatment and of data generated in pain models, has suggested that, in DO, a mechanism of action based solely on the inhibition of ACh-mediated muscular contraction is too simplistic. Evidence suggests that the sensory pathways involving the urothelium and suburothelium have a significant role in the coordination of bladder activity. BoNT/A treatment has been shown to reduce raised levels of sensory receptors in suburothelial nerve fibres, but not in the urothelium, without causing a degeneration of the fibres themselves. No signs of significant histologic changes in muscle-fibre density, muscle atrophy, or other degenerative changes have been noted following BoNT/A treatment. In contrast to the effects seen with skeletal muscle, limited evidence of axonal sprouting following BoNT/A treatment has been seen in the detrusor muscle, further supporting differences in the BoNT/A mechanism of action between skeletal and smooth muscles.