Resveratrol suppresses bone cancer pain in rats by attenuating inflammatory responses through the AMPK/Drp1 signaling.

ABSTRACT

Bone cancer pain (BCP) is induced by primary bone cancer and secondary bone metastasis. During BCP pathogenesis, activated spinal astrocytes release proinflammatory cytokines, which participate in pain information transmission. In this study, we found that BCP rats showed disruption of trabecular bone structure, mechanical allodynia, and spinal inflammation. Moreover, reduced adenosine monophosphate-activated protein kinase (AMPK) activity, increased mitochondrial fission-associated protein Drp1 GTPase activity accompanied by the dysfunction of mitochondrial function, and abnormal BAX and Bcl-2 expression were found in the spinal cord of BCP rats. Notably, these alterations are reversed by resveratrol (Res) administration. Cell experiment results demonstrated that Res promotes mitochondrial function by activating AMPK, decreasing Drp1 activity, and inhibiting tumor necrosis factor-α-induced mitochondrial membrane potential reduction. Taken together, these results indicate that Res suppresses BCP in rats by attenuation of the inflammatory responses through the AMPK/Drp1 signaling pathway.