Effects of doxorubicin on neuropathic pain in chronic sciatic nerve constriction injury rats and its underlying mechanism / 中国药理学通报

ABSTRACT

Aim To observe the analgesic effect of doxorubicin ( DOX) on chronic sciatic nerve constric-tion injury (CCI) rat model, and analyze the underly-ing mechanism from the ultrastructure of sciatic nerve ganglion and the expressions of some apoptotic pro-teins.Methods A total of 60 SD rats were randomly divided into four groups sham operation group ( Sham ) , CCI model group ( Model ) , sham operation+DOX 5 mg· kg -1 group ( Sham+DOX) , CCI mod-el +DOX 5 mg· kg -1 group (Model+DOX).DOX was given by caudal vein injection after model estab-lishment .Sham group and model group were given the same amount of saline . The mechanical withdrawal threshold and thermal withdrawal latency were deter-mined by behavioral test .The ultrastructural changes of L4-5 DRG were examined by light microscopy and scanning electron microscopy , respectively .The pro-tein expression levels of Bax , Bcl-2 , PKCɑ, PKCδand PKCε in DRG tissues were determined by Western blot.Results The fluorescence of DOX was found in DRG after DOX was given intravenously .In compari-son with sham group , the thermal and mechanical pain thresholds had no obvious changes in sham +DOX group, while the thresholds were decreased obviously seven days after surgery in model group .In comparison with model group , the pain thresholds in model +DOX group increased significantly , which lasted for the en-tire observation time of six days .The ultra-structure of tissues was damaged obviously in both sham +DOX group and model+DOX group.The protein expression of Bax/Bcl-2 increased, while the expressions of PKCδand PKCεdecreased with DOX injection .Conclusions DOX can retrograde and reach the DRG tissues after intravenous administration . The attenuation effect of DOX on neuropathic pain is related to the apoptosis in-duced by the down-regulation of PKCδ and PKCε in DRG cells.