Papers of the Week

Bone cancer pain (BCP) is common in patients with advanced cancers as tumors metastasize to bone. Pathogenesis of BCP is complex and poorly understood which leads to inefficiency of clinical treatment. During pathological pain status, astrocytes are activated and release various inflammatory cytokines, which result in the development of peripheral and central sensitization. As energy factory, mitochondria undergo frequent fusion and fission and play essential role for astrocyte function. 2-bromopalmitate (2-BP) is an inhibitor of protein palmitoylation, and its function on BCP was unclear. In this paper, we aimed to investigate the potential curative effects and mechanisms of 2-BP on bone cancer pain. BCP rat model was established through intratibial inoculation of rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats. As a result, BCP rats exhibited bone destruction and sensitive nociceptive behavior. And increased leukocyte infiltration, activation of astrocytes, and imbalance of mitochondrial fission and fusion dynamics were observed in spinal cord of BCP rats. Intrathecal 2-BP administration significantly attenuated pain behavior of BCP rats. Meanwhile, 2-BP administration reduced spinal inflammation, reversed spinal mitochondrial fission and fusion dynamic imbalance, and further inhibited spinal mitochondrial apoptosis in BCP rats. In C6 cell level, 2-BP treatment decreased Drp1 expression and increased OPA1 expression in a dose-dependent manner, and inhibited CCCP-induced mitochondrial membrane potential change. These data illustrated that 2-BP attenuated bone cancer pain by reversing mitochondrial fusion and fission dynamic imbalance in spinal astrocytes.