Effects of doxorubicin on neuropathic pain in chronic sciatic nerve constriction injury rats and its underlying mechanism
10.3969/j.issn.1001-1978.2018.01.009
- VernacularTitle:阿霉素减轻坐骨神经慢性缩窄性损伤大鼠的神经病理性疼痛及其机制
- Author:
feng Lin HE
1
;
xin Ke WANG
;
Lei LEI
;
jian Yong ZHANG
;
wen Su SU
Author Information
1. 河北医科大学药理学教研室
- Keywords:
doxorubicin;
dorsal root ganglion;
CCI;
apoptosis;
PKC;
neuropathic pain
- From:
Chinese Pharmacological Bulletin
2018;34(1):33-38
- CountryChina
- Language:Chinese
-
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.
