**1.3 General indications**

*Neurostimulation and Neuromodulation in Contemporary Therapeutic Practice*

receptors to produce bladder wall contraction.

of neurologic lower urinary tract dysfunction [1].

by relaxation of the urinary sphincters and pelvic floor.

by preganglionic fibers arising from T11-L2. Their main function is inhibition of bladder wall contraction and excitation of the internal urethral sphincter, both necessary to maintain continence and facilitate urinary storage. Parasympathetic efferents which originate preganglionically from the sacral spinal cord through the S2 to S4 spinal nerve roots reach postganglionic fibers in the pelvic plexus and bladder wall and through stimulation of release of acetylcholine act on muscarinic

Afferent innervation from the bladder consists of small myelinated Aδ fibers, which relay information via the pelvic and pudendal nerves to the sacral spinal cord at S2 to S4 about the properties of a bladder contraction, and synapse with spinal interneurons and autonomic fibers constituting what is known as the micturition reflex arc. The interneurons also relay information to higher centers, namely the periaqueductal gray and pontine micturition centers, as well as the hypothalamus, thalamus, prefrontal cortex and angulate gyrus in the cerebrum, among other areas. These centers have a modulatory voluntary control over bladder function and what is perceived by us from somatic sensation in the bladder and pelvic floor, such as sensation of bladder fullness. Bladder afferents also consist of unmyelinated C-fibers which are inactive in normal circumstances but are responsible for transmission of noxious stimuli such as bladder pain and are involved in the development

During the phase of urinary storage, information about increasing bladder volume and pressure is carried by afferent discharges that stimulate both the sympathetic and parasympathetic preganglionic fibers. While the stimulated parasympathetic fibers would elicit a bladder contraction, their activity is inhibited by sympathetic discharges at the postganglionic level, which also maintain contraction of the internal urethral sphincter at the level of the bladder neck and contraction of the pelvic floor in response to bladder filling. This coordination of afferent and efferent pathways ensures stable bladder filling and urinary storage and subsequently continence. Beyond a certain threshold of bladder filling, afferent discharges trigger the micturition reflex at the pontine level. This reflex results in inhibition of sympathetic and efferent continence signals and allowance of parasympathetic mediated bladder contractions to facilitate bladder emptying, preceded

Any interruption at the gross or microcellular level of these neural circuits would result in voiding dysfunction, be it by increased bladder sensation resulting in urinary frequency as is the case in overactive bladder and urgency-frequency disorders, loss of continence as in urgency urinary incontinence, loss of bladder sensation or inability to generate a voiding pressure as in non-obstructive urinary retention, or formation or upregulation of pathological neural circuits for reflex bladder activity or transmission of noxious stimuli such as is neurogenic bladder or

**1.2 Mechanisms of action of neuromodulation of lower urinary tract**

Neuromodulation of the lower urinary tract aims to restore lost or dysfunctional neural functions to fulfill the two main functions of the bladder, storage and voiding. Artificial stimulators directly or indirectly apply electrical stimulation that achieves this purpose. Through continuous or intermittent electrical stimuli at different nerves and sites, neuromodulation treats both bladder over- and under-activity, as

The modes by which these electrical stimulations achieve such restoration differ from one type of neuromodulation to the other, and this will be further discussed in

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each section.

pelvic pain disorders.

well as pelvic and bladder pain [5].

Neuromodulation in urology is aimed at control of uninhibited bladder contractions to eliminate sensation of urgency and provide appropriate urinary continence. This is the scenario for overactive bladder disease and neurogenic bladder overactivity. Inability to void resulting in urinary retention is also corrected by neuromodulation, though the literature has been less evident for neurogenic causes of retention versus the established restorative effects on voiding in idiopathic non-obstructive urinary retention (NOUR). Other effects through action on shared nerves between the lower urinary tract and the pelvic floor musculature are less reported on and are yet to be approved, but results have shown consistent alleviation of pelvic pain and sexual dysfunction parameters.
