ABSTRACT
Objective To evaluate the role of spinal dopamine D2 receptors in a rat model of neuropathic pain.Methods Thirty healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-200 g,wcre randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),sham operation group (group S),neuropathic pain group (group NP),normal saline group (group N) and dopamine D2 receptor agonist quinpirole group (group Q).Neuropathic pain was produced by chronic constriction injury of the sciatic nerve (CCI) in rats anesthetized with intraperitoneal 2％ pentobarbital sodium 40 mg/kg.At 7 days after CCI,normal saline 10 μl was injected intrathecally over 30 s in group N,and quinpirole 10 μg (in 10 μl of normal saline) was injected intrathecally over 30 s in group Q.At 1 day before CCI,3 and 7 days aher CCI,and 30 min and 1,2,4,8 and 16 h after administration,mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.Results There was no significant difference in MWT and TWL at each time point between group C and group S.MWT was significantly lower,and TWL was shorter at T1-8 in NP,N and Q groups than in C and S groups.Compared with group N,no significant change was found in MWT and TWL at each time point in N group,and MWT was significantly increased,and TWL was prolonged at T4-6 in group Q.Conclusion Inhibited function of spinal dopamine D2 receptors is involved in the maintenance of neuropathic pain in rats.
ABSTRACT
Objective To investigate the effects of Aktl gene knockout on pain behavior induced by chronic constriction injury model of sciatic nerve (CCI).Methods C57BL/6 male mice were randomly divided into Akt1 knockout group (KO group,n=12),wild type group(WT group,n=12).All mice were made model of CCI in the right sciatic nerve.Each mouse received tests of the paw withdrawal mechanical threshold (PWMT) and the paw withdrawal thermal latency(PWTL) at the times of 1d before and 1 d,3 d,5 d,7 d,10 d,14 d,17 d,21 d after surgery.Results For both KO group and WT group,the basic values of PMWT(right(0.89±0.15)g,(0.87±0.15)g; left(0.97±0.19) g,(1.05±0.14) g,P＞0.05) and PWTL(right (7.64±0.71) s,(7.56±0.68) s ;left: (7.67±0.6) s,(7.64±0.64) s,P＞0.05) showed no significantly statistical difference.Compared with WT group and the basic value,PWMT and PWTL were significantly decreased after surgery in KO group (P＜0.05).The PWMT and P WTL of the left paw in KO group and WT group had no obvious statistical difference (P＞0.05).However,the PWMT and PWTL of the right paw significantly decreased in the two groups compared with left paw.Conclusion h aggravates the neuropathic pain induced by CCI in mice when the Akt1 gene was knocked out.
ABSTRACT
Objective To investigate the effects of repeated intrathecally kinesin superfamily protein 17 (KIF17) antisense oligodeoxynucleotide (ODN) on the expression of mLin10 and NR2B in spinal cord in a mouse model of bone cancer pain.Methods Fifty-six male C3H/HeJ mice,aged 4 ～ 6 weeks,weighting 20 ～ 25 g,were randomly divided into two groups:sham operation group (group S,n=20) and bone cancer pain group (group T,n=36).20μl α-minimal essence medium (α-MEM) which containing 2× 105 NCTC2472 osteosarcoma cells was injected into the intramedullary space of the right femur in group T.In group S,no cancer cell was instead.The number of spontaneous flinches (NSF) and the paw withdrawal mechanical threshold (PWMT) were measured at the day before (base) and the days 4,7,10 and 14 after inoculation.According to the corresponding time points,twenty-four mice were sacrificed for determination the expression of KIF17,mLin10 and NR2B using Western blot.Then,the mice of group T were randomly divided into three groups (n=8,T1,T2,T3,group).In group S and group T1,Saline 5 μl was injected intrathecally.KIF17 sense ODN and antisense ODN,5 μg/5μl were respectively injected in group T2 and T3 for 6 consecutive days.Pain behaviors were assessed at the days 2-6 after the first injection.And determinated the KIF17,mLin10 and NR2B expression,again.Results Compared with group S,the NSF was increased and the PWMT was decreased at the days 7,10 and 14 after inoculation in group T (P＜0.05).Compared with the base ((0.65±0.15),(1.06±0.06),(1.01±0.14)),the expression of KIF17,mLin10 and NR2B (14d:(1.13 ±0.06),(2.17 ± 0.37),(1.85 ± 0.32)) were increased at the days 7,10 and 14 after inoculation in group T(P＜0.05).During the course of the injection,compared with group T1 and T2,the NSF was decreased and the PWMT was increased significantly in the group T3(P＜0.05),the expression of KIF17,mLin10 and NR2B((0.88±0.08),(0.96±0.11),(1.03±0.08)) were reduced in group T3 (P＜0.05).Conclusion Intrathecal KIF 17 antisense ODN in the mice of bone cancer pain improves the pain behaviors,and inhibits the up-regulated of KIF17,mLin10 and NR2B during the course of the injection.