In summary, in the present study, we demonstrate that EA at ST36 and ST37can alleviate visceral and somatic hypersensitivity in TNBS-induced PI-IBS model mice, which is probably related to the decreased expression of Epac1 and Piezo2 both in the colon and L5–S2 DRGs, and the reduced 5-HT release and 5-HT3R expression. Here, PIEZO2 is linked to irritable bowel syndrome.