Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery

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dc.contributor.authorColdwell, J.
dc.contributor.authorPhillis, B.
dc.contributor.authorSutherland, K.
dc.contributor.authorHowarth, G.
dc.contributor.authorBlackshaw, L.
dc.date.issued2007
dc.description.abstract5-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.
dc.description.statementofresponsibilityJonathan R. Coldwell, Benjamin D. Phillis, Kate Sutherland, Gordon S. Howarth, and L. Ashley Blackshaw
dc.identifier.citationThe Journal of Physiology, 2007; 579(1):203-213
dc.identifier.doi10.1113/jphysiol.2006.123158
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.orcidHowarth, G. [0000-0001-6979-6084]
dc.identifier.orcidBlackshaw, L. [0000-0003-1565-0850]
dc.identifier.urihttp://hdl.handle.net/2440/37066
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.source.urihttps://doi.org/10.1113/jphysiol.2006.123158
dc.subjectColon
dc.subjectAfferent Pathways
dc.subjectNerve Fibers
dc.subjectSplanchnic Nerves
dc.subjectMast Cells
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectColitis
dc.subjectDisease Models, Animal
dc.subjectSerotonin
dc.subjectCalcitonin Gene-Related Peptide
dc.subjectPhysical Stimulation
dc.subjectElectrophysiology
dc.subjectRecovery of Function
dc.subjectCell Degranulation
dc.subjectAction Potentials
dc.subjectBiomarkers
dc.titleIncreased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery
dc.typeJournal article
pubs.publication-statusPublished

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