Botulinum toxin and urinary bladder disorders in women: new insight into an old problem

Abstract

The overactive bladder (OAB) and painful bladder (bladder pain syndrome/interstitial cystitis) syndromes are common urological problems that frequently co-exist and severely affect the quality of life of many women. As yet, the pathophysiology of both conditions is incompletely understood, and therefore the results of available treatment including drug therapy are usually disappointing. Botulinum neurotoxin type A (BoNT-A) is increasingly used in humans for pharmaceutical and cosmetic purposes. The toxin is produced from fermentation of the bacterium Clostridium botulinum. Due to ease of administration and relatively long-lasting effects, BoNT-A is now widely used in clinical practice amongst several medical specialties, particularly in dermatology and plastic surgery mainly for cosmeceutical rejuvenation [1]. More recently, there is abundant literature supporting the use of BoNT-A in urology and urogynecology, and the off-label use of this drug continues to grow in both disciplines worldwide. Although the first use of BoNT-A in lower urinary tract disorders was reported 22 years ago [2], evidence-based information to guide current urogynecologic practice is still lacking. BoNT-A has unique physio-pharmacological properties that includes a muscle-paralyzing effect via inhibition of acetyl-choline release from motor nerves into the neuromuscular junction. This induces temporary chemodenervation that produces relaxation of both skeletal and smooth muscles. Another potentially very important property of BoNT-A is the ability to inhibit afferent neurotransmission inhibition. This leads to a very potent analgesic effect by inhibition of ATP secretion, reduced production of substance P, and reduced axonal expression of capsaicin, purinergic receptors, and nerve growth factors [3]. The therapeutic rationale for using BoNT-A in lower urinary tract disorders in women is primarily based on both the muscle relaxant and analgesic actions. Anticholinergic agents are the mainstay of pharmacologic treatment of OAB because of the ability to reduce bladder contractions and associated symptoms in most patients. These drugs are, however, associated with poor tolerability and relatively poor patients’ compliance because of the high incidence of anticholinergic adverse effects such as dry mouth, blurred vision, and constipation. In fact, almost 17% of participants withdrew from clinical trials of anticholinergic drugs because of this reason alone [4]. Over the past two decades, the use of cystoscopic intra-detrusor injection of BoNT-A has revolutionized the treatment of OAB, particularly the intractable symptoms associated with neurogenic OAB induced by spinal cord lesions and diseases [5]. Challenging cases of neurogenic OAB that are often associated with poor control of symptoms on standard E. Kocjancic (*) Department of Urology, College of Medicine, University of Illinois at Chicago, 840 S Wood Street, Chicago, IL 60612, USA e-mail: ekocjanc@uic.edu