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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/18/4517    most recent jphysiol.2008.156984v1 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 Google Scholar Articles by Keating, C. Articles by Grundy, D. PubMed PubMed Citation Articles by Keating, C. Articles by Grundy, D. Related Collections Alimentary

¹ Department of Biomedical Sciences, University of Sheffield, Sheffield, UK
² Wolfson Digestive Diseases Research Unit, Queens Medical Centre, University of Nottingham, Nottingham, UK

Visceral hypersensitivity is an important clinical feature associated with irritable bowel syndrome which in some patients has been linked to prior infection. Here we employ an animal model in which transient infection leads to persistent gut dysfunction to investigate the role of altered 5-HT metabolism upon afferent mechanosensensitivity in the post-infected gut. Jejunal segments isolated from Trichinella spiralis-infected mice were used to assess 5-HT metabolism whilst afferent activity in T. spiralis-infected mice was studied by extracellular recordings from jejunal mesenteric afferent bundles and patch clamp recordings of isolated nodose ganglion neurons (NGNs). During acute infection, intestinal 5-HT content and release increased, 5-HT turnover decreased and afferent discharge in response to mechanical stimulation was attenuated. By day 28 post infection (PI), 5-HT turnover had normalized, but 5-HT content and release were still elevated. This was associated with afferent mechano-hypersensitivity, which persisted for 8 weeks PI and was susceptible to 5-HT₃ receptor blockade. NGNs from post-infected animals were more excitable than controls but their current densities in response to 2-methyl-5-HT were lower. T. spiralis infection increased mucosal 5-HT bioavailability and affected the spontaneous activity and mechanosensitivity of gastrointestinal sensory nerves. This involved an initial hyposensitivity occurring during acute infection followed by long-term hypersensitivity in the post-infectious period that was in part mediated by 5-HT acting via 5-HT₃ receptors. Functional down-regulation of 5-HT₃ receptors also occurs in the post-infected animals, which may represent an adaptive response to increased mucosal 5-HT bioavailability.

(Received 15 May 2008; accepted after revision 17 July 2008; first published online 24 July 2008)
Corresponding author D. Grundy: Department of Biomedical Sciences, Florey Building, University of Sheffield, Sheffield, S10 2TN, UK.  Email: d.grundy{at}sheffield.ac.uk