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


METHODS
C57Bl6 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.


RESULTS
Afferent firing to serosal 5-HT (500 μM) 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 μM) 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
Afferent 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.
Department of Surgery, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany. mueller.mario@charite.de.
M H
MH
Mueller
Department of Gastroenterology, Ludwig-Maximilian's University, Munich, Germany.
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X
Zhao
Department of Surgery, Ludwig-Maximilian's University, Munich, Germany.
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T
Macheroux
Department of Surgery, Josephinum Hospital, Munich, Germany.
M S
MS
Kasparek
Department of Surgery, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany.
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H
Seeliger
Department of Surgery, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany.
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ME
Kreis
D000818:Animals; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D007415:Intestinal Obstruction / Q000378:metabolism* / Q000503:physiopathology*; D007421:Intestine, Small / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism*; D009924:Organ Culture Techniques
D018836:Inflammation Mediators
Small bowel obstruction; afferent intestinal neuronal sensitivity; inflammatory pathways