**Abstract**

Urological applications of neuromodulation and neurostimulation are among the most evolving fields for these technologies. First approved for management of refractory urge incontinence, different modalities of neuromodulation and stimulation have been tested, applied and verified for a vast spectrum of voiding and pelvic floor dysfunction disorders. The modalities of delivering this treatment have also evolved in the last three decades, with a focus on sacral neuromodulation. The experimental and established "off-label" applications of neuromodulation have also encompassed chronic pelvic pain disorders, including chronic prostatitis and bladder pain syndrome, among others. In this chapter, we discuss all the hypothesized theories suggested on how this technology provides therapeutic potential for a number of chronic and debilitating urological conditions, the modes of delivery be it anterior, sacral, and posterior tibial to name a few, and the evolving and future applications.

**Keywords:** neuromodulation, sacral neuromodulation, posterior tibial nerve stimulation, lower urinary tract dysfunction

### **1. Introduction**

Neuromodulation in urological practice is not a novel concept, but certainly one that has lagged in dissemination. The first reports of the use of neuromodulation to stimulate bladder emptying date back to as early as the 1970s, although the results back then were disappointing [1]. It was not until 1988 that Schmidt and Tanagho restarted the discussion on applications of neuromodulation and electrical stimulation of the sacral nerve in urology, and since then reports on different novel techniques and applications ensued [2, 3]. The term "neurostimulation" was recoined later to "neuromodulation," as experts in the neuro-urology field argued that electrical currents do not only stimulate but rather modulate the messages carried by different nerves involved in the micturition reflex and the lower urinary tract [4].

### **1.1 Review of lower urinary tract innervation and processes of storage and micturition**

The urinary bladder has both afferent and efferent innervation. Efferent innervation is both sympathetic and parasympathetic. The hypogastric nerve carries postganglionic sympathetic fibers innervated at the inferior mesenteric ganglion

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 receptors to produce bladder wall contraction.

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 of neurologic lower urinary tract dysfunction [1].

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 by relaxation of the urinary sphincters and pelvic floor.

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 pelvic pain disorders.

### **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 well as pelvic and bladder pain [5].

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 each section.

**211**

*Neuromodulation in Urology: Current Trends and Future Applications*

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

The spectrum of neuromodulation modalities in urology has evolved yet focuses around two manners that correspond to our understanding of the innervation of the lower urinary tract and pelvic floor muscles: sacral neuromodulation, by sacral anterior root stimulation, sacral nerve modulation and recently pudendal nerve stimulation (PNS) and its derivatives, and less invasive neuromodulators and peripheral nerve stimulators, the most studied of which is posterior tibial nerve stimulation.

Though this mode of urological neuromodulation is almost of historical interest in the face of current advances in the field and the dominance of sacral neuromodulation, it yet deserves honorable mention as it paved the way to utilize the sacral region for restoration of bladder function. Through stimulation of the anterior sacral nerve, both bladder parasympathetic efferents and somatic motor fibers to the external urethral sphincter are activated. This ventral activation facilitates

Brindley in 1976 implanted intradurally and bilaterally on the ventral roots from S2 to S5 subcutaneous cables that were externally powered and would provide ondemand electromagnetic stimulation to facilitate voiding [5–7]. He later modified his procedure by performing posterior rhizotomy at the S2–S3 level during implantation of the stimulator to improve the continence outcome by eliminating the effect C-fiber bladder afferents had on amplifying the micturition reflex. This is what was later named the Brindley procedure, and its popularity phased out years later as more studies and reports demonstrated debilitating and unacceptable complications such as sacral dermatome hyperalgesia, cerebrospinal fluid leak, and damage to the anterior nerve root. The procedure, however, remains indicated for patients with complete spinal cord injury (SCI) with maintained bladder reflexes [1, 7–9].

The first reports describing the application of sacral neuromodulation were by Schmidt and Tanagho, the latter concentrating on its application in neurogenic lower urinary tract dysfunction [2, 3]. Since then, both experimental and approved applications and research aiming to understand the mechanism of action by which sacral neurostimulation, or more appropriately now termed sacral neuromodulation (SNM), affects and rehabilitates the functions of the lower urinary tract, both in facilitating bladder storage and voiding, has expanded. Researchers also embarked

*DOI: http://dx.doi.org/10.5772/intechopen.92287*

**1.3 General indications**

sexual dysfunction parameters.

**2.1 Sacral anterior root stimulation**

intermittent bladder emptying [1].

**2.2 Sacral neuromodulation**

**2. Neuromodulation modalities in urology**
