Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO)

Mueller, M. H.; Zhao, X.; Macheroux, T.; Kasparek, M. S.; Seeliger, H. und Kreis, M. E. (2016): Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO). In: Neurogastroenterology and Motility, Bd. 28, Nr. 10: S. 1599-1608

Abstract

BackgroundSmall bowel obstruction (SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment. MethodsC57Bl6 mice were anesthetized, and a midline laparotomy was performed. A small bowel loop was ligated 5 cm proximal to ileo-cecal valve to induce SBO. Control animals received a sham midline laparotomy. SBO animals and controls were sacrificed after 3, 9, or 24 h (each n = 6). A dilated segment of small intestine located 1.5 cm oral to the ligature was prepared for multi-unit mesenteric afferent nerve recordings in vitro. Histological assessment of leukocyte infiltration was performed by myeloperoxidase (MPO). Pro-inflammatory cytokine expression was quantified by RT-PCR. Data are mean SEM. Key ResultsAfferent firing to serosal 5-HT (500 M) peaked at 3.9 +/- 0.2 impulse/s 24 h after induction of SBO compared to 2.4 +/- 0.1 impulse/s in sham controls (p < 0.05). Serosal bradykinin (0.5 M) led to an increase in peak afferent firing of 5.3 +/- 0.5 impulse/s in 24 h SBO animals compared to 3.5 +/- 0.2 impulse/s in sham controls (p < 0.05). No differences in 5-HT and BK sensitivity were observed in 3 and 9 h SBO animals compared to controls. Continuous mechanical ramp distension of the intestinal loop was followed by a pressure-dependent rise in afferent nerve discharge that was reduced in 3 h SBO animals compared to sham controls (p < 0.05). MPO stains showed a rise in leukocyte infiltration of the intestine in SBO animals at 9 and 24 h (p < 0.05). Il-6 but not TNF-a gene expression was increased at 9 and 24 h in SBO animals compared to sham controls (p < 0.05). Conclusions & InferencesAfferent nerve sensitivity is increased 24 h after induction of SBO. SBO led to a delayed onset intestinal inflammatory response. Inflammatory mediators released during this inflammatory response may be responsible for a later increase in afferent sensitivity. Agents with anti-inflammatory action may, therefore, have a beneficial effect during SBO and may subsequently help to prevent possible organ dysfunction.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1350-1925
• Sprache: Englisch