Luteolin relieves lung cancer-induced bone pain by inhibiting NLRP3 inflammasomes and glial activation in the spinal dorsal horn in mice

Abstract

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.

Keywords: Cancer-induced bone pain; Glial cells; Luteolin; MAPKs; NLRP3 inflammasome; Spinal dorsal horn.