CXCL1-CXCR2 signaling mediates the activation of microglia in the nucleus tractus solitarii to promote pancreatic cancer-induced pain. (PubMed, Brain Behav Immun)
In mice with pancreatic cancer-induced pain, the microglia activation in the NTS was observed, characterized by increased cell density and decreased process number and length, while injection of microglia inhibitor minocycline in the NTS alleviated pancreatic cancer-induced pain...Blocking CXCL1-CXCR2 signaling by injection of CXCL1 neutralizing antibody or CXCR2 antagonist SB225002 in the NTS of mice with pancreatic cancer-induced pain alleviated abdominal hypersensitivity and hunching behavior, and also reversed the activation of neurons and microglia. Additionally, injection of recombinant CXCL1 in the NTS of sham-operated mice induced abdominal pain, and activated the neurons and microglia. In summary, our study highlights the critical role of NTS microglia activation mediated by CXCL1-CXCR2 signaling in pancreatic cancer-induced pain.