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Increased responsiveness of rat colonic splanchnic afferents to 5‐HT after inflammation and recovery
Author(s) -
Coldwell Jonathan R.,
Phillis Benjamin D.,
Sutherland Kate,
Howarth Gordon S.,
Blackshaw L. Ashley
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.123158
Subject(s) - inflammation , splanchnic , stimulation , medicine , endocrinology , receptor , bradykinin , 5 ht receptor , serotonin , neurogenic inflammation , splanchnic nerves , mast cell , substance p , neuropeptide , immunology , blood flow
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 EC 50 was reduced from 3.2 × 10 −6 to 8 × 10 −7 m in acute inflammation and recovered to 2 × 10 −6 m after recovery. Responsiveness to mechanical stimulation was unaffected. 5‐HT 3 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‐HT 3 receptors and mast cells.