**1. Introduction**

Botulinum toxin (BoNT), one of the most potent natural neurotoxins known for centuries, has been found with emerging medical efficacy in the past few decades [1,2]. BoNT was initially documented with the symptoms of foodborne botulism in the 18th century [3]. A botulism outbreak after a funeral dinner with smoked ham in 1895 led to the discovery of the pathogen Clostridium botulinum by Emile Pierre van Ermengem, Professor of Bacteriology at the University of Ghent [3]. Acute BoNT poisoning was initially observed with vomiting, intestinal spasms, mydriasis, ptosis, dysphagia, and finally respiratory failure [4]. It may take 3–6 months to recover from botulinum intoxication [4]. Since BoNT was discovered as the produced toxin from the bacterium Clostridium botulinum, it has been widely used to treat neuropathic pain syndromes and dystonic disease [5–8].

Botulinum toxin A (BoNT-A) has been used for the treatment of lower urinary tract disease (LUTD) since the late 1980s. Dykstra et al. reported injection of BoNT-A to the external urethral sphincter in men with spinal cord injury (SCI) for the treatment of detrusor-sphincter dyssynergia (DSD) in

1988 [9]. The treatment of SCI patients with neurogenic detrusor overactivity (DO) using detrusor BoNT-A injections at multiple sites was also developed [10]. Idiopathic DO and overactive bladder (OAB) patients were also reported with successful treatment with intravesical BoNT-A injection [11,12]. Maria et al. first described the therapeutic effects of BoNT-A injection for patients with benign prostatic hyperplasia (BPH) with voiding dysfunction in 2003 [13]. However, the latest randomized controlled trial investigating the efficacy of BoNT-A injection for BPH-related lower urinary tract symptoms (LUTS) demonstrated no significant difference between the treatment group and the placebo [14]. Moreover, BoNT-A intravesical injection treatment has been developed for interstitial cystitis/bladder pain syndrome (IC/BPS) because of its anti-inflammatory effects [15,16]. As the uses of BoNT-A expand in the field of urology, understanding its mechanisms and clinical effects is essential.
