Luteolin Relieves Lung Cancer-Induced Bone Pain by Inhibiting NLRP3 Inflammasomes and Glial Activation in the Spinal Dorsal Horn in Mice.

BACKGROUND:Bone cancer pain (BCP) is one of the most severe complications in cancer patients. However, the pharmacological therapeutic approaches are limited. Luteolin, a major component of flavones, is widely distributed in plants and plays a critical role in the antinociceptive effects, but whether luteolin could alleviate cancer pain and its underlying mechanisms are not known.HYPOTHESIS/PURPOSE:This study investigated the molecular mechanisms by which luteolin reduced BCP.METHODS:Behavioral, pharmacological, immunohistochemical, and biochemical approaches were used to investigate the effect of luteolin on BCP.RESULTS:Luteolin treatment ameliorated Lewis lung cancer (LLC)-induced bone pain in mice in a dose-dependent manner. Luteolin treatment could inhibit the activation of neurons, glial cells, and NOD-like receptor protein 3 (NLRP3) inflammasomes in the dorsal spinal cord in the BCP mouse model. Furthermore, phosphorylated p-38 mitogen-activated protein kinase (MAPK) in the spinal dorsal horn (SDH) was suppressed by luteolin treatment that could influence the analgesic and glial inhibition effects of luteolin.CONCLUSION:Our results demonstrated that luteolin inhibited neuroinflammation by obstructing glial cell and NLRP3 inflammasome activation via modulating p38 MAPK activity in SDH, ultimately improving LLC-induced BCP.