Effect of intrathecal rapamycin on diabetic neuropathic pain in rats
10.3760/cma.j.issn.0254-1416.2014.01.013
- VernacularTitle:鞘内注射雷帕霉素对大鼠糖尿病神经痛的影响
- Author:
Wanyou HE
;
Hanbing WANG
;
Chengxiang YANG
;
Jian HE
;
Weicheng ZHAO
;
Wenxuan ZHANG
- Publication Type:Journal Article
- Keywords:
Sirolimus;
Injections,spinal;
Diabetes mellitus;
Neuralgia
- From:Chinese Journal of Anesthesiology
2014;34(1):47-50
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of intrathecal rapamycin on diabetic neuropathic pain in rats.Methods Thirty adult male Sprague-Dawley rats,weighing 180-220 g,in which IT catheters were successfully implanted,were randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),diabetic neuropathic pain group (group DN),rapamycin 1 μg group (group R1),rapamycin 3 μg group (group R3) and rapamycin 10 μg (group R10).Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg on 5 days after IT catheters were implanted in DN,R1,R3 and R10 groups.Citric acid-sodium citrate buffer 6 ml/kg was injected intraperitoneally in group C.In R1,R3 and R10 groups,rapamycin (dissolved in 10 μl 4％ dimethyl sulfoxide) 1,3 and 10 μg were intrathecally injected,respectively,once a day for 7 consecutive days starting from day 21 after STZ injection,while the equal volume of 4％ dimethyl sulfoxide was given instead in C and DN groups.Paw withdrawal threshold (PWT) to yon Frey filament stimulation was measured before IT catheters were implanted,before STZ injection,on 7,14 and 21 days after STZ injection,and on 1,3,5 and 7 days after rapamycin administration.After measurement of PWT,the rats were sacrificed and L2-5 segments of the spinal cord were removed for determination of the expression of mTOR and phosphorylated mTOR (p-mTOR),S6K and phosphorylated S6K (p-S6K) (by Western blot) and expression of mTOR mRNA and S6K mRNA (by RT-PCR).Results Compared with group C,MWT was significantly decreased at 14 and 21 days after STZ injection in DN,R1,R3 and R10 groups,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was up-regulated in group DN (P ＜ 0.01).Compared with group DN,MWT was significantly increased at 5 and 7 days after rapamycin administration in group R1,at 3,5 and 7 days after rapamycin administration in group R3,and at 1,3,5 and 7 days after rapamycin administration in group R10,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was down-regulated in R1,R3 and R10 groups (P ＜ 0.01).Conclusion Intrathecal rapamycin can alleviate diabetic neuropathic pain in rats.
