To understand the role of the P2Y12 receptor in the comorbidity of visceral pain and depression, we used P2Y12 short hairpin (shRNA) to interfere with the expression of P2Y12 in the mPFC of IBD mice and then assessed visceral pain and depression-like behavior changes, as well as the protein expression of IL-1β and the activity state of microglia in the mPFC of IBD mice. This evidence concerns the gene P2RY12 and irritable bowel syndrome.