ABSTRACT
Objective To investigate the effect of curcumin on the expression of cannabinoid receptor 1 (CBR1) and NR2B subunit-containing NMDA receptor in spinal cord dorsal horn and dorsal root ganglion (DRG) neurons in a rat model of neuropathic pain.Methods Seventy-two male Sprague-Dawley rats,weighing 200-230 g,were randomly divided into 4 groups ( n =18 each):sham operation group (S group),chronic constrictive injury (CCI) group,curcumin group (Cur group) and solvent control group (SC group).Neuropathic pain was induced by CCI.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals in groups CCI,Cur and SC.Curcumin was injected intraperitoneally at 100 mg· kg- 1· d-1 for 14 consecutive days after operation in Cur group,while the equal volume of dimethyl sulfoxide was given instead of curcumin in SC group.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured on 2 days before operation and on 1,3,7,10 and 14 days after operation.Six rats in each group were sacrificed on 3,7 and 14 days after operation and the lumbar segments of the spinal cord ( L4,5 ) and DRGs were removed to determine the expression of CBR1 and NR2B by immuno-histochemistry.Results Compared with S group,MWT was significantly decreased,TWL was significantly shortened,and the expression of CBR1 and NR2B in spinal cord dorsal horn and DRG neurons was up-regulated after operation in the other three groups (P ＜ 0.05 ).Compared with CCI group,MWT was significantly increased,TWL was significantly prolonged,the expression of CBR1 inspinal cord dorsal horn and DRG neurons was up-regulated,and the expression of NR2B in spinal cord dorsal horn and DRG neurons was down-regulated after operation in group Cur (P ＜ 0.05 ),and no significant change in the parameters mentioned above was found in group SC ( P ＞ 0.05 ).Conclusion Curcumin can alleviate neuropathic pain in rats,and up-regulation of CBR1 expression and down-regulation of NR2B expression in spinal cord dorsal horn and DRG neurons are involved in the mechanism.
ABSTRACT
Objective To investigate the effect of curcumin on apoptosis in hippocampal neurons and the expression of c-Jun N-terminal kinase 3 (JNK3) and postsynaptic density protein 95 (PSD95) in hippocampus during cerebral ischemia-reperfusion (I/R) in rats with spontaneous hypertension (SH) .Methods One hundred and thirty-five male rats (homologous with WKY) with SH and 90 male normotensive WKY rats, weighing 275-325 g,were used in this study. The WKY rats were randomized into 2 groups ( n = 45 each) : sham operation group (WS group) and cerebral I/R group (W-I/R group) . The rats with SH were randomly divided into 3 groups ( n = 45each) : sham operation group (S-S group), cerebral I/R group (S-I/R group) and curcumin group (S-C group) .Global cerebral ischemia was produced by 4 vessel-occlusion method. The bilateral common carotid arteries were only exposed but not ligated in W-S and S-S groups. Intraperitoneal corn oil 10 ml/kg was injected at 30 min of reperfusion in W-I/R and S-I/R groups. Intraperitoneal curcumin 100 mg/kg was injected at 30 min of reperfusion in S-C group. Three animals in each group were sacrificed at 2 h, 6 h, 1 d, 3 d and 7 d of reperfusion and their brains were harvested for determination of apoptosis in hippocampal neurons and the expression of JNK3 and PSD95in hippocampus. Results The number of apoptotic neurons was significantly increased in S-S group compared with W-S group ( P < 0.05) . The number of apoptotic neurons was significantly increased and the expression of JNK3was up-regulated in S-I/R group compared with S-S group ( P < 0.05) . The number of apoptotic neurons was significantly decreased and the expression of JNK3 was down-regulated in S-C group compared with S-I/R group (P <0.05) . There was no significant difference in the expression of PSD95 among all the groups ( P > 0.05) . Conclusion Curcumin can inhibit apoptosis in hippocampal neurons and the mechanism is related to down-regulation of the expression of JNK3 in hippocampus. The mechanism by which curcumin down-regulates the expression of JNK3in hippocampus may not be related to PSD95 pathway.