In this pancreatitis-related pain model, adult monocyte-derived macrophages migrate into the pancreatic tissue during the early stage of tissue damage or inflammation, and secrete HMGB1, which in turn activates RAGE and accelerates CXCL12/CXCR4 signaling, resulting in pancreatic pain (Figure 6). Here, CXCR4 is linked to pancreatitis.