Visceral Pain
Klaus Bielefeldt | G.F. Gebhart
Chronic visceral pain is very common. Abdominal pain
is among the main reasons for physician visits, with more
than 12 million consultations occurring each year in the
United States.1 Patients with visceral pain present unique
challenges because the pain is often poorly localized and is
associated with strong autonomic reactions and changes in
visceral function. Pain management, in turn, may further
alter visceral function, with opioid effects on the gastroin-
testinal tract providing a good example. These unintended
treatment effects on visceral function can exacerbate the
pain or lead to additional discomfort, thus showing that
rational and effective pain management needs to be based
on an understanding of the anatomic and physiologic basis
of visceral function and pain.
PHYSIOLOGIC BASIS OF VISCERAL
SENSATION AND PAIN
ANATOMY AND PHYSIOLOGY OF VISCERAL
AFFERENT PATHWAYS
Most viscera arise from midline structures and thus receive
bilateral innervation. As a result, visceral stimuli activate
both hemispheres of the brain, with a predominance of
the left side in most right-handed individuals.2,3 In addi-
tion, organs in the chest cavity and most viscera within
the abdomen receive dual afferent innervation, with vagal
and spinal nerves conveying sensory input to the central
nervous system (Fig. 32.1). Although vagal fibers do not
reach the pelvic organs, the distal part of the colon, blad-
der, prostate, and uterus also have a complex sensory
innervation, with afferents projecting through the thora-
columbar (hypogastric) and lumbosacral (pelvic) nerves
to the spinal cord.
The vagus nerve is predominantly composed of afferent
fibers (≥80%) that project via the nodose and jugular ganglia
to the nucleus of the solitary tract in the brainstem. Spinal
afferents pass through prevertebral (sympathetic) ganglia to
the dorsal root ganglia and send their endings to the dorsal
horn and central gray matter of the spinal cord. Informa-
tion about noxious stimuli is relayed rostrally through the
spinothalamic tract. In addition, postsynaptic dorsal horn
neurons within the central gray send their central processes
through the medial aspect of the dorsal columns, a pathway
that has only recently been recognized as being uniquely
important in visceral pain.4
Most physiologic studies characterizing the properties
of visceral sensory pathways rely on responses to defined
mechanical stimuli. Vagal afferents form a relatively
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homogeneous group that is activated by low-intensity
mechanical stimuli and encodes stimulus intensity over a
wide range. The low threshold of activation is consistent
with the presumed role of these sensory pathways in the
regulation of physiologic processes. In contrast, two classes
of mechanosensitive spinal afferents can be distinguished
by their response characteristics: low-threshold fibers are
similarly activated by low-intensity stimuli and continue
to encode stimulus intensity over a wide range, whereas
high-threshold fibers are activated by intense, potentially
noxious intensities of mechanical stimuli. Thus, spinal
high-threshold fibers resemble specialized nociceptors
that have been described and characterized best in the
skin, thus suggesting that they play a primary role in vis-
ceral nociception.5,6 However, because mechanosensitive
visceral afferents encode stimulus intensity over a wide
range and can become sensitized after a visceral insult, it
is likely that both low- and high-threshold mechanosensi-
tive afferents can contribute to visceral pain conditions.
Finally, most visceral sensory neurons are polymodal,
which means that they respond to multiple stimulus
modalities, including endogenous and exogenous chemi-
cals contained in luminal contents, temperature (heat or
cold), and stretch.
MUCOSAL SIGNALING AND VISCERAL SENSATION
In the airways, gastrointestinal tract, and urinary bladder,
nerve fibers are found in close proximity to epithelial cells,
which often exhibit specializations consisting of secretory
vesicles on the basal surface.7-9 This structural organization
and functional studies suggest that visceral epithelial cells
function as an interface between chemical or mechanical
stimuli and the nervous system. The best example is sero-
tonin released from enteroendocrine cells in the gastroin-
testinal tract. The gut is the major source of this signaling
molecule and contains 95% of the body’s serotonin. Much
of this serotonin is stored in specialized enteroendocrine
(enterochromaffin) cells and can be released by chemi-
cal or mechanical stimuli to activate intrinsic and extrinsic
neurons.7 Within the urinary tract, epithelial cells release
adenosine triphosphate, which acts on purinergic recep-
tors (P2X receptors) and is involved in normal micturition,
as well as in bladder pain.10 Finally, bladder epithelial cells
also express the capsaicin receptor transient receptor poten-
tial vanilloid-1 [TRPV1]), an ion channel that is activated
by acid, temperature, endogenous lipid mediators, and the
pungent substance (capsaicin) contained in hot peppers.
Animals with a targeted deletion of this channel display
altered micturition behavior, again pointing to the impor-
tance of epithelial cells in visceral sensation.11
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