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ALIMENTARY |
1 Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
2 Discipline of Physiology
3 Department of Medicine
4 Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia 5000, Australia
5 Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia
6 School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide, Australia
7 School of Biological Sciences, Flinders University, South Australia, Australia
5-Hydroxytryptamine (5-HT) activates colonic splanchnic afferents, a mechanism by which it has been implicated in generating symptoms in postinfectious and postinflammatory states in humans. Here we compared mechanisms of colonic afferent activation by 5-HT and mechanical stimuli in normal and inflamed rat colon, and after recovery from inflammation. Colonic inflammation was induced in rats by dextran sulphate sodium. Single-fibre recordings of colonic lumbar splanchnic afferents revealed that 58% of endings responded to 5-HT (10–4 M) in controls, 88% in acute inflammation (P < 0.05) and 75% after 21 days recovery (P < 0.05 versus control). Maximal responses to 5-HT were also larger, and the estimated EC50 was reduced from 3.2 x 10–6 to 8 x 10–7 M in acute inflammation and recovered to 2 x 10–6 M after recovery. Responsiveness to mechanical stimulation was unaffected. 5-HT3 receptor antagonism with alosetron reduced responses to 5-HT in controls but not during inflammation. Responses to the mast cell degranulator 48/80 mimicked those to 5-HT in inflamed tissue but not in controls, and more 5-HT-containing mast cells were seen close to calcitonin gene-related peptide-containing fibres in inflamed serosa. We conclude that colonic serosal and mesenteric endings exhibit increased sensitivity to 5-HT in inflammation, with both an increase in proportion of responders and an increase in sensitivity, which is maintained after healing of inflammation. This is associated with alterations in the roles of 5-HT3 receptors and mast cells.
(Received 19 October 2006;
accepted after revision 27 November 2006;
first published online 30 November 2006)
Corresponding author L. A. Blackshaw: Nerve-Gut Research Laboratory, Level 1, Hanson Institute, Frome Road, Adelaide, South Australia 5000, Australia. Email: ashley.blackshaw{at}adelaide.edu.au
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