Effect of DREAM on GLT-1 expression in spinal cord in rats with bone cancer pain and morphine tolerance
10.3760/cma.j.issn.1008-1372.2014.12.003
- VernacularTitle:DREAM对骨癌痛-吗啡耐受大鼠脊髓谷氨酸转运体-1表达的影响
- Author:
Peng YU
;
Wangpin XIAO
;
Hongmei ZHOU
;
Zhigang CHENG
;
Yunjiao WANG
;
Qinghe ZHOU
;
Cheng WU
- Publication Type:Journal Article
- Keywords:
Gene expression regulation,neoplastic;
Bone neoplasms/complications;
Pain/etiology;
Morphine/pharmacology;
Drug tolerance;
Glutamic acid/metabolism
- From:
Journal of Chinese Physician
2014;16(12):1593-1597
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of downstream regulatory element antagonist modulator (DREAM) on the expression of glutamate transporter-1 (GLT-1) in spinal cord in rats with bone cancer pain and morphine tolerance.Methods Sixty female healthy Sprague-Dawley (SD) rats weighing 200 ～230 g were randomly divided into tow groups,group Ⅰ cancer pain (CP,n =48) and group Ⅱ Sham (S,n =12).Cancer pain in each group was produced by inoculation of syngenetic Walker 256 rat mammary gland carcinoma cells (5 × 105) to left tibia.Pain threshold to mechanical stimulus was measured before (baseline) and after the surgical procedure.From 14 d to 18 d after the inoculation of carcinoma cells,36 rats from group CP received subcutaneous injection of morphine at 3 times per day with doses increasingly from 10 mg/kg initially to 20 mg/kg,30 mg/kg,40 mg/kg,and 60 mg/kg.Equal volume of normal saline was applied to the 12 rats left in group CP.On 19th day after the carcinoma cells inoculation once subcutaneous injection of morphine at 3mg/kg was performed in all rats in group CP.From the next day,the rats in group CP ever receiving injections of morphine for 5 days were randomized into thre subgroups,including subgroups morphine tolerance (MT,n =12),vehicle (V,n =12),and RNAi (R,n =12).They were injected intrathecally with 20 μl of normal saline (NS),10 μl vehicle plus 10 μ1 NS,and 10 μ1 of DREAM-shRNA plus l0 μ1 NS,respectively,once a day for 5 days.Focusing on the affected limb,mechanical pain threshold was measured one day before surgery (T0),and at day7 (T1),day 14 (T2),day 18 (T3),day 19 (T4),day21 d (T5),day 25 (T6),and day 28 (T7) after surgery.The animals were sacrificed at day 28 after the procedure.The lumbar 4 segments in rats were removed for detection of DREAM and GLT-1.Results The mechanical threshold was significantly decreased at T1 compared to the baseline in all groups,returned to the baseline at T2 ～ T7 in group S,at T4 in group CP,and at T2 in group MT,V,and R,but remained low at T5 ～T7 in group CP,and at T3 ～T7 in group MT,V,and R.Compared to that at T1,it was decreased at T2 ～T3 and T5 ～ T7 in group CP,at T4 ～ T7 in group MT and V,and at T4 ～ T5 in group R,going back to the baseline at T4 in group CP and at T2 in group MT,V and R,and increased at T6 ～ T7 in group R.Compared to that in group S,the mechanical threshold in group CP,MT,V and R was decreased,and lower at T2 in group CP and at T4 in group MT,V and R.Compared to that in group CP,the mechanical threshold was significantly higher at T2 ～ T3 but lower at T4 in group MT,V,and R,decreased at T5 in group R and at T5 ～ T7 in group MT and V.The mechanical threshold was increased at T6 ～ T7 in group R and higher than that in groups MT and V.The expression of DREAM,compared to that in group S,was down-regulated in other groups.Compared to group CP,increment was shown in groups MT and V,and decrease was exhibited in group R.It was cut down in group R compared to that in groups MT and V.Compared to group S,GLT-1 was decreased in other groups.It was down-regulated in groups MT,V and R compared to group CP.Conclusions DREAM is involved in the development of allodynia after morphine tolerance in rats with bone cancer pain.No evidence in this study supports a link between DREAM and GLT-l in spinal cord.
