Nervous System Innervation of the Lower Urinary Tract

Three sets of peripheral nerves have a significant role in LUT function. These nerves include the sacral parasympa-thetics, the thoracolumbar sympathetics, and the sacral somatic nerves.

Autonomic Innervation

The parasympathetic nervous system's general role in LUT function is to facilitate emptying. The parasympathetic efferent fibers originate in the intermediolateral region of the gray matter within the sacral cord (S2-4) and emerge as preganglionic fibers from the ventral root. The pelvic nerve conveys these fibers to the LUT.

Acetylcholine is the primary neurotransmitter at the ganglia and the effector sites. The receptors of this system are muscarinic and nicotinic. There are five subtypes of known muscarinic receptors (M1-M5) and they are located on all autonomic effector cells. In the human bladder there is a predominance of M2 receptors. The M3 receptors are primarily responsible for bladder contractions. There are no known muscarinic receptors specific for the bladder. The muscarinic receptors are the targets of anticholiner-gics for the treatment of the overactive detrusor. The nico-tinic receptors are located on autonomic ganglia and the motor end plates of skeletal muscle. Atropine competitively inhibits these muscarinic sites. High doses of nicotine inhibit nicotinic sites.

The sympathetic nervous system's general role in LUT function is to facilitate storage of urine. The efferent fibers of this system originate in the intermediolateral region of the gray matter within the thoracolumbar spinal cord (T10-L2). These nerves traverse the paravertebral ganglia and join the hypogastric plexus anterior to the aorta. This plexus divides into the right and left hypogastric nerves. These merge with the pelvic nerve to form a pelvic plexus or inferior hypogastric plexus. The primary neurotrans-mitters of the sympathetic nervous system are acetyl-choline and norepinephrine. Acetylcholine is released at the ganglion and norepinephrine (adrenergic) at the effector sites. There are two primary types of receptors (alpha and beta) in the sympathetic nervous system and they are characterized on the basis of differential effects elicited by catecholamines. The alpha receptors are stimulated by nor-epinephrine and methoxamine, but not isoproterenol. When stimulated, alpha receptors elicit smooth muscle contraction. Two subtypes of alpha receptors exist, A1 and A2. These receptors are located throughout the bladder, but are predominantly in the bladder base and neck. Stimulation of alpha receptors increases outlet resistance (i.e. phenylpropanolamine). Alpha receptors are not as prominent in the female urethra and bladder neck as they are in the male. Beta receptors are stimulated the most by isoproterenol, less by epinephrine, and least by norepi-nephrine. When stimulated, beta receptors elicit an inhibitory effect on detrusor muscle contraction. Two subtypes of beta receptors exist, B1 and B2. Beta 1 receptors are located in the cardiovascular system. The beta 2 receptors are located throughout the bladder, but to a greater extent are within the bladder body. Beta receptor stimulation in the LUT inhibits bladder contraction and causes receptive relaxation of the detrusor to allow for increasing bladder volumes, without increasing intravesical pressure (detrusor compliance).

Somatic Innervation

The somatic nervous system originates in efferent fibers of S2-S4, which form the pudendal nerve. The pudendal nerve in turn innervates the striated sphincter and the pelvic floor. The motor ganglia are located in the anterior horn of the spinal cord and the primary neurotransmitter is acetylcholine. The receptors of the somatic system are nicotinic and their activity is blocked by curare.

Sensory Innervation

Sensory innervation of the bladder is via the pelvic and hypogastric nerves. Sensory input from the urethra is through the pudendal nerve. The tachykinins are the primary neurotransmitters and include substance P, and neurokinin A and B. These neurotransmitters relay their messages through A delta and C fibers. A delta fibers are finely myelinated, located in smooth muscle, and sense bladder fullness. The C fibers are unmyelinated, located in the mucosa and muscle, and sense nociception and overdistention of the detrusor. Up-regulation of these fibers is thought to be one of the possible etiologies of bladder pain. Other neurotransmitters of the nervous system that are thought to have a key role in LUT function are listed below.

Detrusor contractions

Prostaglandins Detrusor relaxation

Adenosine 5'-triphosphate Opioids Urethral relaxation Nitric oxide Opioids Urethral contraction Serotonin Epinephrine Supporters of micturition

Gamma-aminobutyric acid (inhibitory) Enkephalins (inhibitory) Glutamate (facilitative) Dopamine (facilitative)

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