The overall conclusion of all those studies is that mast cell mediators, and particularly tryptase, are released in significantly higher amounts in the tissues of IBS patients. In their study, Barbara et al. demonstrated that in IBS patients, mast cells lie closer to nerve fibers of the mucosa compared with those in control patients (42). This suggests that once released by degranulating mast cells, tryptase could be in direct contact with enteric or primary afferent nerves, both of which express PAR2 (5–7, 33, 44, 45), and induce hyperexcitability