The effect of PGC-1α mediates mitochondrial biogenesis on bone cancer pain and concurrent mirror-image pain
Objective:To investigate the effects and mechanisms of peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)regulated mitochondrial biogenesis on bone cancer pain and concurrent mirror-image pain.Methods:In the first part of the experiment,adult female SD rats were randomly divided into 2 groups using a table of random numbers,Sham group and BCP(bone cancer pain)group,with 10 rats in each group.In the second part of the experiment,the rats were randomly divided into 3 groups using a table of random numbers,Sham+vehicle group,BCP+vehicle group,BCP+ZLN(ZLN005,PGC-1α activator)group,with 25 rats in each group.MRMT-1 breast cancer cells were injected into the medullary cavity of the left tibia to establish BCP rat model,and Sham group rats were injected with equal volume of Hank's balanced salt solution.In the second part of the experiment,rats in the ZLN group were injected intrathecally with ZLN005(100 μg/30 μl),and the Sham group and vehicle group rats were injected with an equal volume of vehicle.The levels of PGC-1α,Nrf1,and Tfam in the spinal cord of the rats were analysed by western blot.The mtDNA copy number expression was analysed by qPCR.The localization of PGC-1α was analysed by immunofluorescence.Results:Mechanical hyperalgesia was induced in the bilateral hind paws of rats by intra-bone marrow injection of cancer cells.Intrathecal injection of ZLN005 attenuated mechanical hyperalgesia of BCP rats.In the spinal cord of BCP rats,a decreased in levels of PGC-1α,Nrf1,Tfam and relative mtDNA copy number were observed.The expression of PGC-1α,Nrf1,Tfam and relative mtDNA copy number was elevated after administration with ZLN005.The distribution of PGC-1α in the spinal dorsal horn was demonstrated on both sides.The fluorescence intensity of PGC-1α was declined in BCP rats.PGC-1α was mainly located in neurons.Conclusion:In the spinal cord,damage to mitochondrial biogenesis facilitated the development of bone cancer pain concomitant with mirror-image pain.PGC-1α activation can alleviate bone cancer pain and concurrent mirror-image pain by promoting mitochondrial biogenesis.
bone cancer painmirror-image painmitochondrial quality controlmitochondrial biogenesisPGC-1α
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