title: Mast cells and the cyclooxygenase pathway mediate colonic afferent nerve sensitization in a murine colitis model.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathophysiology, Shandong University, Medical School, Shandong, China.
authors: B
authors: B
authors: Xue
authors: M H
authors: MH
authors: Müller
authors: J
authors: J
authors: Li
authors: T
authors: T
authors: Pesch
authors: M S
authors: MS
authors: Kasparek
authors: A
authors: A
authors: Sibaev
authors: M
authors: M
authors: Hausmann
authors: G
authors: G
authors: Rogler
authors: M E
authors: ME
authors: Kreis
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000294:innervation / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000294:innervation / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000378:metabolism*; D055366:Synaptic Potentials / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D017833:Visceral Afferents / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin