Gastrointestinal (GI) functions are controlled by a dynamic interplay among different
cell types that interact through a variety of signaling molecules in communication
with the central nervous system. The enteric nervous system (ENS) exerts a major regulatory
role on gut function via functionally distinct classes of neurons (e.g., intrinsic
primary afferent neurons, interneurons, motorneurons). Smooth muscle cells form an
electrical syncytium within the gut and are innervated, directly or indirectly through
interstitial cells of Cajal (ICCs), by neurons. ICCs have an active role in the control
of motility as pace-makers and through mechanosensitive ion channels. Also, the immune
system and enteric glia, are now increasingly understood to be actively involved in
the modulation of GI function. Any noxa affecting the integrity of these cell types,
alone or in combination, may evoke dysfunction as identified in a number of clinically
recognized conditions characterized by severe impairment of GI motility and transit
(e.g., chronic intestinal pseudo-obstruction - CIPO). Pathological abnormalities underlying
severe GI dysmotility can be classified into three major entities: neuropathies, “mesenchymopathies”
(i.e., changes in ICCs), and myopathies. Although rare, enteric neuro-ICC-myopathies
are of primary importance for gastroenterologists and clinicians because they markedly
affect the patient’s quality of life and they may be so severe to be life-threatening.
Genetic, environmental and inflammatory mechanisms are now recognized to play a role
in neuro-ICC-myopathies underlying severe GI dysfunction. This translational knowledge
may help to develop effective and targeted therapeutic strategies for patients suffering
from CIPO or other severe chronic bowel disorders.
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© 2015 Published by Elsevier Inc.