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Practical Urology: EssEntial PrinciPlEs and PracticE

bladder volume during the filling phase. In addi-

muscle by releasing ACh acting on muscarinic

tion, some afferents originate in dorsal root

receptors. However, an atropine-resistant (non-

ganglia at the thoracolumbar level and travel in

adrenergic, non-cholinergic: NANC) contractile

the hypogastric nerve. The sensory nerves to

component is regularly found in the bladders of

the striated muscle of the external urethral

most animal species.1 Such a component can

sphincter travel in the pudendal nerve to the

also be demonstrated in functionally and mor-

sacral region of the spinal cord.5 After entering

phologically altered human bladder tissue, but

the spinal cord, the primary afferent fibers of

contributes only up to a few percent to normal

the pelvic and pudendal nerves travel rostrally

detrusor contraction.13 ATP is one important

in Lissauer’s tract, and are connected to second

mediator of the NANC contraction,14 although

order neurons.

the involvement of other transmitters cannot be

The most important afferents for the micturi-

ruled out.13 The pelvic nerve also conveys para-

tion process are myelinated Ad-fibers and unmy-

sympathetic nerves to the outflow region and

elinated C-fibers travelling in the pelvic nerve to

the urethra. These nerves exert an inhibitory

the sacral spinal cord,6,7 conveying information

effect on the smooth muscle, by releasing nitric

from receptors in the bladder wall. The Ad-fibers

oxide (NO), and other transmitters.13

respond to passive distension and active con-

traction, thus conveying information about

Sympathetic Nerves

bladder filling.8,9 The activation threshold, i.e.,

the intravesical pressure at which humans report

Most of the sympathetic innervation of the blad-

the first sensation of bladder filling, is for Ad-

der and urethra originates from the intermediolat-

fibers 5–15 cm H2O.10 C-fibers have a high

eral nuclei in the thoraco-lumbar region (T10-L2)

mechanical threshold and respond primarily to

of the spinal cord. The axons leave the spinal cord

chemical irritation of the bladder urothelium/

via the splanchnic nerves and travel either through

suburothelium11 or cold.12 Following chemical

the inferior mesenteric ganglia (IMF) and the

irritation, the C-fiber afferents exhibit sponta-

hypogastric nerve, or pass through the paraverte-

neous firing when the bladder is empty and

bral chain to the lumbosacral sympathetic chain

increased firing during bladder distension.

ganglia and enter the pelvic nerve. Thus, sympa-

These fibers are normally inactive and are there-

thetic signals are conveyed in both the hypogastric

fore termed “silent fibers.”

nerve and the pelvic nerve.5 The preganglionic

sympathetic transmission is, like the parasympa-

Efferent Signaling

thetic preganglionic transmission, predominantly

mediated by ACh acting on nicotinic receptors.

Parasympathetic Nerves

Some preganglionic terminals synapse with the

postganglionic cells in the paravertebral ganglia or

Contraction of the detrusor smooth muscle and

in the IMF, while other synapse closer to the pelvic

relaxation of the outflow region result from

organs, and short postganglionic neurones inner-

activation of parasympathetic neurones located

vate the target organs. Thus, the hypogastric and

in the sacral parasympathetic nucleus (SPN) in

pelvic nerves contain both preand postgangli-

the sacral spinal cord at the level of S2–S4.5 The

onic fibers.5 The predominant effect of the sympa-

axons pass through the pelvic nerve and syn-

thetic innervation is to contract the bladder base

apse with the postganglionic nerves either in

and the urethra. In addition, the sympathetic

the pelvic plexus, in ganglia on the surface of

innervation inhibits the parasympathetic path-

the bladder (vesical ganglia), or within the walls

ways at spinal and ganglionic levels too.In humans,

of the bladder and urethra (intramural ganglia).

noradrenaline is released in response to electrical

The preganglionic neurotransmission is pre-

stimulation in vitro, and the normal response to

dominantly mediated by acetylcholine (ACh)

released noradrenaline is relaxation.1 However,the

acting on nicotinic receptors, although the

importance of the sympathetic innervation for

transmission can be modulated by adrenergic,

relaxation of the human detrusor has never been

muscarinic, purinergic, and peptidergic pre-

established. In contrast, in several animal species,

synaptic receptors.10 The postganglionic neu-

the adrenergic innervation has been demonstrated

rones in the pelvic nerve mediate the excitatory

to mediate relaxation of the detrusor during

input to the normal human detrusor smooth

filling.