HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 579/1/203    most recent jphysiol.2006.123158v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coldwell, J. R. Articles by Blackshaw, L. A. Search for Related Content PubMed PubMed Citation Articles by Coldwell, J. R. Articles by Blackshaw, L. A. Related Collections 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

This article has been cited by other articles:

				X.-C. Zhang, A. M. Strassman, R. Burstein, and D. Levy Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 806 - 812. [Abstract] [Full Text] [PDF]