The Mast Cell–PAR2–TRP Axis: A Convergent Mechanism for Visceral Hypersensitivity Independent of Divergent Motility in IBS

Most patients with irritable bowel syndrome have diarrhea or constipation, two opposite bowel habits. Although defecation habits represent opposing phenotypes, patients across all subtypes exhibit visceral hypersensitivity. This review explores the common pathway that causes visceral hypersensitivity: the mast cell-PAR2-TRP axis. The mechanism involves tryptase released by mast cells. Furthermore, tryptase activates PAR2, which sensitizes downstream TRP ion channels that conduct pain signals. The review also examines the factors leading to the formation of different fecal characteristics. In terms of treatment, this review also summarizes therapeutic agents targeting different components of this axis. Future pharmaceutical research should focus more on the mast cell-PAR2-TRP axis.