Intrathecal Injection Of Roscovitine Ease The Ccd Rats Pain And Spinal Dorsal Angle Nr2a Protein Expression

Objective To investigate the analgesic effects of intrathecal injection of roscovitine in rats with chronic neuropathic pain and the expression level of NR2A in the Spinal cord dorsal horn.Methods The rat model of chronic compression of dorsal root ganglia(CCD) was developed by a constant oppression on the spinal cord dorsal root ganglia(DRG) with a stainless steel rod (4 mm in longth,0.7 mm in diameter) inserted into the intervertebral foramen between L4-6.All the rats(n=54) were divided randomly into three groups:groupS(n=18),groupC(n=18) and groupR(n=18). The group R was further divided randomly into 3 groups: R1(n=6),R 2(n=6) and R3(n=6). The group C was further divided randomly into 3 groups: C1(n=6),C 2(n=6) and C3(n=6). The group S was further divided randomly into 3 groups: S1(n=6),S2(n=6) and S3(n=6).On the 7 d,the rats of group R2 and R3 were intrathecally injected roscovitine 50μg dissolved in 50%DMSO 10μl. The rats in group C2,C3,S2 and S3 were intrathecally injected 50%DMSO 10μl only. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested before operation,on the 7 d day after operation and at 2 h,24 h,72 h after intrathecal injection in the group S3,C3 and R3.All the rats were tested the expression levels of NR2A in the Spinal cord dorsal horn by the means of immunohistochemistry after being killed.Results (1) the obvious decreasing of PWMT were observed on 7 d before the administration of Roscovitine in group C3 (3.50±0.77)g and group R3 (3.64±0.40)g compared with group S3 (11.31±1.13)g and preoperative base level in group C3 (13.25±2.21)g and group R3 (14.38±1.53)g (P < 0.01); the obvious decreasing of PWTL were also observed on 7 d before the administration of Roscovitine in group C3 (8.91±1.08)s and group R3 (9.28±1.18)s compared with group S3 ( 18.45±1.44)s and preoperative base level in group C3 (18.59±1.92)s and grouph R3 (18.34±1.23)s(P<0.01) .(2) The significant increasing of PWMT in group R3 were observed at the 24 h (7.32±0.69)g after the administration compared with group C3 (3.86±1.14) g and d7 level in group R3 (3.64±0.40) g (P<0.05) . (3) The significant increasing of PWTL in group R3 were observed at the 2 h (15.46±1.51)s after the administration compared with group C3 (9.91±1.07) s and d 7 level in group R3 (9.28±1.18) s (P<0.05) . The expression of NR2A receptor in the DRG was significantly lower in group R(0.21±0.02) from 24 h to 72 h after drug injection than that in group C(0.26±0.01) (P<0.05).Conclusion Intrathecal injection of roscovitine could efficiently attenuate mechanical neuropathic pain in rats with CCD,which might be related to its inhibitory effect on the expression of NR2A receptor in the DRG.