Sensory Effects of Antimuscarinics: Still a Matter of Debate

Abstract

osensitivity. It is now recognized that lower urinary tract symptoms (LUTS) is a global term that encompasses all urinary symptoms, including voiding, storage, and postmicturition symptoms [1]. Storage urinary symptoms (or ‘‘failure to store’’) are thought to be more specifically related to detrusor overactivity and are largely encompassed by the term overactive bladder (OAB), although weakness of the urethral sphincter may also participate [2]. Antimuscarinics are the first-line treatment for patients with OAB. Although the clinical efficacy of antimuscarinics in the management of storage LUTS is not to be questioned, discontinuation rates for anticholinergic medications are high [3] due to the fact that they are poorly tolerated and may be associated with substantial adverse effects. Antimuscarinics are traditionally described to act by increasing bladder capacity; however, their effect on storage symptoms is controversial, and their mechanism of action still a matter of continuing debate. A sensory role for urothelial and suburothelial structures, soliciting both bladder afferent signaling and detrusor muscle, has now been established. Numerous inhibitory and stimulatory neurotransmitters and chemical mediators have been identified to interact with a variety of specialized receptors and to participate in signal transduction leading to wider neuroactivation. Among these, a basal release of acetylcholine (ACh) from the urothelium, as well as neuronal sources, has been demonstrated in isolated human bladder. In addition, muscarinic receptors were found in the urothelium and suburothelial myofibroblasts, suggesting a role in urothelial sensory function [4]. ACh released during the storage phase could be expected to enhance themyogenic contractile activity of the detrusor, which in turn can generate afferent signals [5]. It was