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Mast cells and the cyclooxygenase pathway mediate colonic afferent nerve sensitization in a murine colitis model


Xue, B; Müller, M H; Li, J; Pesch, T; Kasparek, M S; Sibaev, A; Hausmann, M; Rogler, G; Kreis, M E (2013). Mast cells and the cyclooxygenase pathway mediate colonic afferent nerve sensitization in a murine colitis model. Autonomic Neuroscience, 174(1-2):47-53.

Abstract

INTRODUCTION: Intestinal inflammation alters colonic afferent nerve sensitivity which may contribute to patients' perception of abdominal discomfort. We aimed to explore whether mast cells and the cyclooxygenase pathway are involved in altered afferent nerve sensitivity during colitis.
METHODS: C57Bl6 mice received 3% dextran-sulfate sodium (DSS) in drinking water for 7 days to induce colitis. Control animals received regular water. On day 8 inflammation was assessed in the proximal colon by morphology and histology. Extracellular afferent nerve discharge was recorded from the mesenteric nerve of a 2 cm colonic segment. Subgroups were treated in vitro with the mast cell stabilizer doxantrazole (10⁻⁴M) or the cyclooxygenase inhibitor naproxen (10⁻⁵M).
RESULTS: DSS colitis resulted in morphological and histological signs of inflammation. At baseline, peak firing was 11±2 imp s⁻¹ in colitis segments and 5±1 imp s⁻¹ in uninflamed control segments (p<0.05; mean ± SEM; each n=6). In colitis segments, afferent nerve discharge to bradykinin (0.5 μM) was increased to 47±7 compared to 23±6 imp s⁻¹ in recordings from non-inflamed control tissue (p<0.05). Mechanosensitivity during luminal ramp distension (0-80 cm H₂O) was increased reaching 24±5 imp s⁻¹ at 80 cm H₂O during colitis compared to 14±2 in non-inflamed controls (p<0.05). Doxantrazole or naproxen reduced afferent discharge to bradykinin and luminal ramp distension in colitis segments to control levels.
CONCLUSION: Intestinal inflammation sensitizes mesenteric afferent nerve fibers to bradykinin and mechanical stimuli. The underlying mechanism responsible for this sensitization seems to involve mast cells and prostaglandins.

Abstract

INTRODUCTION: Intestinal inflammation alters colonic afferent nerve sensitivity which may contribute to patients' perception of abdominal discomfort. We aimed to explore whether mast cells and the cyclooxygenase pathway are involved in altered afferent nerve sensitivity during colitis.
METHODS: C57Bl6 mice received 3% dextran-sulfate sodium (DSS) in drinking water for 7 days to induce colitis. Control animals received regular water. On day 8 inflammation was assessed in the proximal colon by morphology and histology. Extracellular afferent nerve discharge was recorded from the mesenteric nerve of a 2 cm colonic segment. Subgroups were treated in vitro with the mast cell stabilizer doxantrazole (10⁻⁴M) or the cyclooxygenase inhibitor naproxen (10⁻⁵M).
RESULTS: DSS colitis resulted in morphological and histological signs of inflammation. At baseline, peak firing was 11±2 imp s⁻¹ in colitis segments and 5±1 imp s⁻¹ in uninflamed control segments (p<0.05; mean ± SEM; each n=6). In colitis segments, afferent nerve discharge to bradykinin (0.5 μM) was increased to 47±7 compared to 23±6 imp s⁻¹ in recordings from non-inflamed control tissue (p<0.05). Mechanosensitivity during luminal ramp distension (0-80 cm H₂O) was increased reaching 24±5 imp s⁻¹ at 80 cm H₂O during colitis compared to 14±2 in non-inflamed controls (p<0.05). Doxantrazole or naproxen reduced afferent discharge to bradykinin and luminal ramp distension in colitis segments to control levels.
CONCLUSION: Intestinal inflammation sensitizes mesenteric afferent nerve fibers to bradykinin and mechanical stimuli. The underlying mechanism responsible for this sensitization seems to involve mast cells and prostaglandins.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:19 Feb 2014 13:48
Last Modified:08 Dec 2017 04:14
Publisher:Elsevier
ISSN:1566-0702
Publisher DOI:https://doi.org/10.1016/j.autneu.2013.01.001
PubMed ID:23384476

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