“…Thus, our data pave the way for considering the release of these mediators as a potential mechanism contributing to IBS pathophysiology. However, our study has some limitations, and a number of issues remain to be addressed, including the assessment of: (1) mediators (other than histamine and tryptase) of mast cell and nonmast cell origin, which are likely involved in the activation of sensory neurons; (2) participation of mechanical stimuli on the sensitization of sensory fibers; (3) causes underlying the increased release of mucosal mediators involved in sensory neuron activation [eg, psychologic factors, neurohormonal factors (eg, neuropeptides, corticotrophin releasing factor) food allergens, intestinal microflora, intestinal permeability]; (4) potential clinical correlates between sensory neural pathways activation evoked by mucosal mediators and abdominal pain perceived by patients; (5) clinical usefulness of inhibition of mast cell activation (eg, mast cell stabilizers, 36,37 anti-IgE antibodies, 38 inhibitors of the intracellular protein tyrosine kinase, Syk 39 ), or antagonism of the effects of mast cell mediators (eg, histamine and proteases receptor antagonists). These still open issues could represent the objective of future ad hoc-designed studies.…”