**1. Introduction**

Botulinum toxin, one of the most powerful neurotoxins in nature, is produced by the anaerobic, Gram-positive organism, *Clostridium botulinum*. Exposure to the botulinum toxin can be fatal, since this can lead to flaccid paralysis of the muscles, dysautonomia, and subsequent respiratory failure [1]. 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].

Nowadays, 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 a long-time challenge for urologists who treat its multifactorial conditions and accompanying pain. Recently, it was recognized that the disease not only has organ-specific syndromes, but also urogenital manifestations of regional or systemic abnormalities characterized by neuropathic pain [4].

The mechanism of BTX-A activity on bladder pain has been investigated: it possibly affects both afferent and efferent nerves, along with having an antinociceptive mode of action [5]. Here we reviewed current molecular and cellular evidence and related animal studies for a better general understanding of the mechanism of action of BTX-A in bladder pain.
