Intrathecal administration of roscovitine attenuates cancer pain and inhibits the expression of NMDA receptor 2B subunit mRNA

Abstract

Cancer pain is one of the most severe chronic pains. The mechanisms underlying cancer pain are still unclear. Because of the pain-relieving effects of Cdk5 (Cyclin-dependent kinase 5) antagonist roscovitine in inflammation pain models, we tested whether roscovitine would induce antihyperalgesia in cancer pain. Our previous study showed that the NR2B (N-methyl-D-aspartate receptor 2B) in the spinal cord participates in bone cancer pain in mice. In this study, we used a mouse model of bone cancer pain to investigate whether roscovitine could attenuate bone cancer pain by regulating the expression level of NR2B mRNA in spinal cord. C3H/HeJ mice were inoculated into the intramedullary space of the right femur with Osteosarcoma cells to induce ongoing bone cancer pain behaviors. At day 14 after operation, inoculation of Osteosarcoma cells significantly enhanced mechanical allodynia and thermal hyperalgesia, which was attenuated by intrathecal administration of different doses of roscovitine. Correlated with the pain behaviors changes, RT-PCR experiments in our study revealed that there was a marked increase in the expression of NR2B mRNA in spinal cord after operation, which was attenuated by intrathecal administration of roscovitine. These results suggest that roscovitine may be a useful adjunct therapy for bone cancer pain, and NR2B in spinal cord may participate in this effect.