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Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus
Author(s) -
Farro G.,
GomezPinilla P. J.,
Di Giovangiulio M.,
Stakenborg N.,
Auteri M.,
Thijs T.,
Depoortere I.,
Matteoli G.,
Boeckxstaens G. E.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12796
Subject(s) - contractility , carbachol , medicine , inflammation , cholinergic , enteric nervous system , contraction (grammar) , endocrinology , vagus nerve stimulation , ileus , motility , muscle contraction , stimulation , pathogenesis , biology , vagus nerve , microbiology and biotechnology
Background Postoperative ileus ( POI ) is characterized by a transient inhibition of gastrointestinal ( GI ) motility after abdominal surgery mediated by the inflammation of the muscularis externa ( ME ). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI . Methods Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation ( IM ) in mice. Immune‐labeling was used to visualize changes in myenteric neurons. Key Results Intestinal manipulation resulted in an immediate inhibition of GI transit recovering between 24 h and 5 days. In vitro contractility to K + (60 mM) or carbachol (10 −9 to 10 −4 M) was biphasically suppressed over 24 h after IM (with transient recovery at 6 h). The first phase of impaired myogenic contractility was associated with increased expression of TNF ‐α, IL ‐6 and IL ‐1α. After 24 h, we identified a significant reduction in electrical field stimulation‐evoked contractions and relaxations, lasting up to 10 days after IM . This was associated with a reduced expression of chat and nos1 genes. Conclusions & Inferences Intestinal manipulation induces two waves of smooth muscle inhibition, most likely mediated by inflammatory cytokines, lasting up to 3 days after IM . Further, we here identify a late third phase (>24 h) characterized by impaired cholinergic and nitrergic neurotransmission persisting after recovery of muscle contractility. These findings illustrate that POI results from inflammation‐mediated impaired smooth muscle contraction, but also involves a long‐lasting impact of IM on the enteric nervous system.