The quest for appropriate diagnostic tools and therapies for IBS runs in parallel with the different pathogenic mechanisms investigated. One of these mechanisms is visceral hypersensitivity, resulting from a disturbed neuronal signalling at the peripheral and/or central levels.12 Rolland-Fourcade et al3 show, in this issue of Gut, that intestinal epithelial cells (Caco-2 cells) release a trypsin-like activity at the basolateral side of the cells after stimulation with a classical inflammatory stimulus (lipopolysaccharide) or with a stress-related stimulus (epinephrine), and they identified it as trypsin-3. They confirmed the clinical relevance of trypsin-3 by proving its presence in colonic tissue from patients with IBS (all subgroups). Besides, trypsin-3 increased epithelial permeability in the Caco-2 monolayers and increased the excitability of mouse dorsal root ganglia neurons in vitro. Moreover, it induced Ca+2 transients in human submucosal neurons in vitro and caused visceral hyperalgesia in response...
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