Nanoparticulate MgH suppresses TRPM2-mediated NLRP3 inflammasome to relieve bone cancer pain.

BACKGROUND

Bone cancer metastases are the third most common site of cancer spread after lungs and liver. This condition often causes severe pain that impairs patients' physical, psychological, and social well-being. We aimed to explore the potential therapeutic benefits of magnesium hydride (MgH) on bone cancer pain (BCP).

METHODS

A BCP model was established in Wistar rats. Daily oral dosing of 0.5% w/w MgH was administered. Assessment included pain sensitivity, motor coordination, and emotional behaviors. Hippocampal samples underwent RNA sequencing, Western blotting, immunofluorescence, and quantitative RT-PCR.

RESULTS

MgH markedly reduced mechanical hypersensitivity and depressive behaviors in rats with BCP. These effects were linked to suppression of the TRPM2-NLRP3 signaling axis in hippocampal microglia. Additionally, MgH served as an adjuvant to reduce opioid tolerance during fentanyl co-treatment, enabling lower opioid dosages. Collectively, MgH inhibited TRPM2 activation, microglial activation, oxidative stress, and NLRP3 inflammasome formation, which together reduced neuroinflammation and improved therapeutic outcomes.

CONCLUSION

MgH nanoparticles may relieve BCP and comorbid depressive symptoms by inhibiting TRPM2-mediated NLRP3 inflammasome activation in hippocampal microglia.