**Ting-Chun Yeh 1, Po-Cheng Chen 2, Yann-Rong Su <sup>3</sup> and Hann-Chorng Kuo 4,\***


Received: 20 December 2019; Accepted: 31 January 2020; Published: 3 February 2020

**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.

**Keywords:** botulinum toxin A; bladder pain; interstitial cystitis; molecular mechanism

**Key Contribution:** This article comprehensively reviewed molecular mechanisms of the analgesic effects of BTX-A and summarized the properties of BTX-A used to treat bladder pain in both peripheral and central nervous pathways.
