Anatomic Neurourology

Anatomic Neurourology

Annah Vollstedt

Larry T. Sirls

Kenneth M. Peters

Introduction: Neuro-anatomy of the Female Lower Urinary Tract

The lower urinary tract (LUT) has two discrete modes: bladder storage and bladder emptying. These two processes are dependent on the coordination of peripheral, spinal and central neuropathways. Continence, or bladder storage, is maintained by inhibition of detrusor muscle contraction and activation of the external urethral sphincter (EUS). After sensation of a full bladder, voiding, or bladder emptying, is initiated by a neural reflex that causes the EUS to relax and the detrusor muscle to contract. In general, storage of urine is a sympathetic nervous system response and voiding is a parasympathetic response. This can be considered in the context of the flight-or-fight response, with the large sympathetic burst when running from a predator one would not want to leave a trail of urine.

The brain and the spinal cord make up the central nervous system (CNS). The peripheral nervous system (PNS) consists of afferent (sensory) and efferent (motor) neurons that communicate with the CNS. The parasympathetic, sympathetic, and the pudendal nerves are the nerves with afferent and efferent fibers that are involved in the coordination of storage and emptying. Figure 4.1 shows an overview of these neural pathways. Lesions along any of these neural pathways may result in LUT dysfunction. The clinical symptoms that are observed are dependent on the area affected. Application of the knowledge of these complex systems can be used to treat neurologic causes of LUT dysfunction, such as with neuromodulation or nerve rerouting. In this chapter, we discuss these neural pathways as well as some of the pertinent clinical applications.


Efferent nerve fibers send impulses from the CNS to the limbs and organs. The efferent innervation of the female LUT includes the parasympathetic, sympathetic, and pudendal nerves.

The parasympathetic nerves originate in the intermediolateral gray matter of the sacral spinal cord at the level of S2-S4. The axons then travel a long distance within the pelvic nerve to the ganglia (pelvic plexus), which is located immediately adjacent to the end organ (bladder).1,2 The preganglionic and postganglionic parasympathetic fibers release acetylcholine (ACh), which is an excitatory neurotransmitter. ACh acts on the muscarinic receptors on the detrusor muscle, which then results in bladder contractions. There are five subtypes of the muscarinic cholinergic receptor (M1 to M5). The bladder contains M2 and M3 receptors. M2 is the more abundant subtype, but M3 is the primary receptor that mediates detrusor contraction. Activation of M3 receptors triggers intracellular calcium release, whereas activation of M2 receptors inhibits adenylate cyclase. The latter may contribute to bladder contractions by suppressing adrenergic inhibitory mechanisms which are mediated by β-adrenergic receptors and stimulation of adenylate cyclase.3

Because the parasympathetic postganglionic neurons are located in the both the detrusor wall and the pelvic plexus, patients with cauda equina syndrome or pelvic plexus injury may not be completely denervated.4

The preganglionic sympathetic nerves arise from the thoracolumbar spinal cord at the level of T10-L2. The sympathetic efferent nerves to the LUT are located in the bilateral hypogastric nerves.2 These noradrenergic nerves originate in the sympathetic chain ganglia and travel to the inferior mesenteric ganglia and then through the hypogastric nerves to the pelvic ganglia. They provide inhibitory input during bladder filling via β-3 receptors and excitatory input to the urethra and the bladder neck via a-1 receptors during filling/storage, which results in detrusor relaxation and EUS contraction. The primary neurotransmitter for postganglionic sympathetic fibers is norepinephrine, but the primary neurotransmitter for preganglionic sympathetic fibers is ACh.

Figure 4.2 shows the distribution of the sympathetic and parasympathetic contributions to the autonomic pelvic plexus.

The pudendal nerve is a somatic nerve whose efferents innervate the striated muscle of the EUS and the pelvic floor muscles. The nerve bodies originate in Onuf nucleus, along the lateral border of the ventral gray matter at the S2-S4 region of the spinal cord (Fig. 4.3).5

The efferent nerve fibers travel within the pudendal nerve to the EUS.2 Its nerve terminals release ACh, which acts on nicotinic cholinergic receptors within the EUS, causing contraction of the EUS during storage/filling.

During voiding/emptying, activation of the parasympathetic pathway leads to the release of nitric oxide (NO), which causes removal of the adrenergic and somatic cholinergic excitation and relaxation of the urethral smooth muscle.6


Afferent nerves receive information from the sensory organs and transmit the input to the CNS. Afferent nerves have been identified both in the detrusor muscle and the suburothelium.2 The suburothelial afferent nerve fibers form a plexus, with some nerve terminals extending into the urothelium itself. This plexus is more prominent in the trigone and bladder neck compared to the bladder dome.2 The pelvic, hypogastric, and pudendal nerves carry afferent input from the LUT to the lumbosacral spinal cord.7 These peripheral nerves carry both afferent and efferent information between the end organs and the spinal cord.2 The majority of afferent input from the bladder and urethra is transmitted via the pelvic nerve, with a smaller amount carried by the hypogastric nerve. The pudendal nerve carries input from the striated muscle of the EUS and the pelvic floor. The afferent nerves release several different neurotransmitters, including vasoactive intestinal polypeptide, substance P, neurokinins, and calcitonin gene-related polypeptide.2

The primary afferent neurons of the pelvic and pudendal nerves are contained in the sacral dorsal root

ganglia (DRG) (Fig. 4.4).7 The afferent neurons of the hypogastric nerve arise in the lumbar DRG.7 Afferent fibers enter the spinal cord through the dorsal horn and then diverge and project either locally to interneurons or to second-order neurons and then ascend to supraspinal centers in the micturition centers in the brain.8

The pelvic nerve afferent fibers monitor bladder volume and amplitude of bladder contractions. These afferent fibers are made up of myelinated (A-delta) and unmyelinated (C) fibers (Table 4.1). The A-delta fibers are located with the detrusor smooth muscle and communicate a sense of fullness, responding to detrusor stretching during bladder filling and are quiescent when the bladder is empty.9 Compared to the unmyelinated C fibers, the A-delta fibers are more sensitive to increases in volumes and gradually increase in discharge frequency at intravesical pressures less than 25 mm Hg.10,11 The unmyelinated C fibers are located within both the detrusor muscle and the lamina propria, adjacent to urothelial cells.12 Those located in the muscle function as nociceptors, responding to overdistention by discharging at a higher range of physiologic bladder volumes.10 In animal studies, C fibers have been described as mechanoinsensitive and have been termed “silent C fibers” because of the lack of response to normal bladder stretching.7 Instead, they respond to other stimuli, such as cold, chemical, or noxious stimulation like high potassium, low pH, high osmolality, or irritants like capsaicin.13,14,15 In spinal cord injury (SCI) patients, the C fibers can become sensitized leading to a new type of spinal cord reflex that results in aberrant bladder contractions.16 In patients with pelvic pain, there is evidence that neuropathy/inflammation/injury of the bladder/pelvic floor can lead to recruitment of C fibers to form a new functional afferent pathway, which may lead to bladder pain and urgency incontinence.7,17 Thus, C fibers may be important targets for clinical interventions.

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May 1, 2023 | Posted by in GYNECOLOGY | Comments Off on Anatomic Neurourology

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