Curcumin Alleviates Bone Cancer Pain by Inhibiting Satellite Glial Cell Activity via Janus Kinase 1/Signal Transducer and Transcription 3 Pathway Activator.

Abstract

<p>Curcumin is the main active component of Curcuma longa L and has anti-inflammatory, antitumor, and neuroprotective properties, making it a potential candidate for bone cancer pain management. Network pharmacology, molecular docking, and molecular dynamics simulations were used to screen and validate core therapeutic targets of curcumin in bone cancer pain. An in&nbsp;vivo mouse model of bone cancer pain was established via intrafemoral injection of Lewis lung cancer cells. A series of in&nbsp;vivo assays was conducted to evaluate pain sensitivity, bone microstructure, inflammatory cytokines, pain-related neuropeptides, and protein expression levels. In silico analysis verified that curcumin has a strong binding affinity for JAK1 and STAT3. In&nbsp;vivo results demonstrated that curcumin dose-dependently elevated the paw withdrawal threshold and latency, as well as ameliorated bone mineral density and bone destruction. Curcumin also suppressed pro-inflammatory cytokines, substance P, calcitonin gene-related peptides, and inhibited satellite glial cell activation by blocking the JAK1/STAT3 pathway. Notably, JAK1 agonist (RO8191) co-administration markedly reversed the analgesic effects of curcumin. Curcumin targets the JAK1/STAT3 signaling pathway, inhibits satellite glial cell activation, downregulates pro-inflammatory cytokine release, and pain-related neuropeptide expression. Therefore, curcumin exerted a significant analgesic effect against bone cancer pain. Elucidating the analgesic mechanism revealed the core therapeutic targets of curcumin in treating bone cancer pain. This study provides experimental evidence for further research on bone cancer pain.</p>