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dc.contributor.authorPhillis, B.en
dc.contributor.authorMartin, C.en
dc.contributor.authorKang, D.en
dc.contributor.authorLarsson, H.en
dc.contributor.authorLindstrom, E.en
dc.contributor.authorMartinez, V.en
dc.contributor.authorBlackshaw, L.en
dc.identifier.citationNeuroscience Letters, 2009; 459(2):57-61en
dc.descriptionCopyright © 2009 Elsevier Ireland Ltd All rights reserved.en
dc.description.abstractThe vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.en
dc.description.statementofresponsibilityBenjamin D. Phillis, Chris M. Martin, Daiwu Kang, Håkan Larsson, Erik A. Lindström, Vicente Martinez and L. Ashley Blackshawen
dc.publisherElsevier Sci Ireland Ltden
dc.subjectColon; Neurons, Afferent; Splanchnic Nerves; Animals; Rats; Rats, Sprague-Dawley; Colitis; Inflammation; Dextran Sulfate; Sensory System Agents; Analysis of Variance; Physical Stimulation; Microelectrodes; Action Potentials; Dose-Response Relationship, Drug; Male; TRPV Cation Channels; In Vitro Techniquesen
dc.titleRole of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammationen
dc.typeJournal articleen
pubs.library.collectionMolecular and Biomedical Science publicationsen
dc.identifier.orcidBlackshaw, L. [0000-0003-1565-0850]en
Appears in Collections:Molecular and Biomedical Science publications

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