Korean J Urol.  2014 Feb;55(2):81-90. 10.4111/kju.2014.55.2.81.

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

• Yoshimura
• Ogawa T
• Miyazato M
• Kitta T
• Furuta A
• Chancellor MB
• Tyagi P

• KMID: 1988431
• DOI: http://doi.org/10.4111/kju.2014.55.2.81

Abstract

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed.

Keyword

Detrusor overactivity; Lower urinary tract; Nerve growth factor; Overactive urinary bladder

MeSH Terms

Animals
Brain
Humans
Lower Urinary Tract Symptoms
Muscle, Smooth
Muscle, Striated
Nerve Growth Factor
Nervous System
Neuronal Plasticity
Neurotransmitter Agents
Pelvic Pain
Pons
Relaxation
Spinal Cord
Urethra
Urinary Bladder
Urinary Bladder, Overactive
Urinary Tract*
Urination
Nerve Growth Factor
Neurotransmitter Agents

Figure

• 

  FIG. 1 Major preganglionic and postganglionic neural pathways from the spinal cord to the lower urinary tract. The sympathetic hypogastric nerve, emerging from the inferior mesenteric ganglion, stimulates urethral smooth muscle. The parasympathetic pelvic nerve, making synapses onto postganglionic neurons in the pelvic ganglion, stimulates bladder detrusor muscle and inhibits urethral smooth muscle. The somatic pudendal nerve stimulates striated muscle of the external urethral sphincter (EUS). ACh, acetylcholine; NE, norepinephrine; NO, nitric oxide; S2-S4, sacral segments of the spinal cord; T10-L2, thoracolumbar segments of the spinal cord. Adapted from Yoshimura et al. Naunyn Schmiedebergs Arch Pharmacol 2008;377:437-48 [4].

• 

  FIG. 2 Innervation of the lower urinary tract. The parasympathetic pelvic nerve stimulates the bladder detrusor muscle, mediated by muscarinic receptors (M3) being activated by acetylcholine (ACh) and purinergic receptors (P2X1) being activated by adenosine triphosphate (ATP), and relaxes the urethral smooth muscle, mediated by nitric oxide (NO). The sympathetic hypogastric nerve stimulates urethral smooth muscle and inhibits bladder detrusor, mediated by α1-adrenergic and β3-adrenergic receptors, respectively. The somatic pudendal nerve stimulates striated muscle of the external urethral sphincter, mediated by ACh activating nicotinic (N) receptors. NA, noradrenaline. Plus and minus signs in parentheses indicate neural stimulation and inhibition, respectively.

• 

  FIG. 3 Afferent fibers transmitting sensory information from the lower urinary tract to the spinal cord. Glutamate is a neurotransmitter present in both the Aδ- and C-fibers; additional neurotransmitters in the C fibers include substance P and calcitonin gene-related peptide (CGRP). Adapted from Yoshimura et al. Naunyn Schmiedebergs Arch Pharmacol 2008;377:437-48 [4].

• 

  FIG. 4 Major reflex pathways to the lower urinary tract initiating and maintaining urine storage. α1, α-adrenergic receptors; β3, β-adrenergic receptors; N, nicotinic receptors; S2-S4, sacral segments of the spinal cord; T10-L2, thoracolumbar segments of the spinal cord; SYM, sympathetic nerve. Plus and minus signs indicate neural stimulation and inhibition, respectively. Adapted from Yoshimura et al. Naunyn Schmiedebergs Arch Pharmacol 2008;377:437-48 [4].

• 

  FIG. 5 Major reflex pathways from the pontine micturition center in the brainstem to the lower urinary tract via the spinal cord regulating micturition. M3, muscarinic receptors; S2-S4, sacral segments of the spinal cord; T10-L2, thoracolumbar segments of the spinal cord; SYM, sympathetic nerve; PSYM, parasympathetic nerve. Plus and minus signs indicate neural stimulation and inhibition, respectively. Descending inputs from the pontine micturition center inhibit neuronal activity in the sympathetic nervous system and Onuf's nuclei in the spinal cord. Adapted from Yoshimura et al. Naunyn Schmiedebergs Arch Pharmacol 2008;377:437-48 [4].

• 

  FIG. 6 Diagram showing hypothetical mechanisms inducing bladder overactivity, LUTS, and pelvic pain. Bladder dysfunction (1) causes increased production of neurotrophic factors such as NGF or other chemical mediators in the bladder wall (2). NGF is taken up by afferent nerves and transported to DRG cells (3) where it changes gene expression, which leads to changes in functional properties of ion channels and receptors and increased neuronal excitability (4). Increased afferent nerve activity results in enhanced synaptic transmission in the spinal cord (5), leading to LUTS or pelvic pain (6) and bladder overactivity (7). BOO, bladder outlet obstruction; DRG, dorsal root ganglion; LUTS, lower urinary tract symptoms; NGF, nerve growth factor.

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