ABSTRACT
Objective To evaluate the effect of curcumin on the expression of MMP-2 and MMP-9 in the spinal dorsal horn and dorsal root ganglion (DRG) of rats with type 2 diabetic neuropathic pain (DNP).Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 35 mg/kg,and confirmed by fasting blood glucose level ≥ 16.7 mmol/L in male Sprague-Dawley rats.Type 2 DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdraw latency (TWL) measured on day 14 after streptozotocin administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups (n =27 each):type 2 DNP group (group DNP); curcumin group (group Cur); solvent control group (group SC).In Cur and SC groups,curcumin 100 mg/kg and corn oil 4 ml/kg were injected intraperitonally,respectively,once a day for 14 consecutive days starting from day 14 after streptozotocin administration.Another 27 normal Sprague-Dawley male rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before type 2 DNP was induced,after type 2 DNP was induced,and at 3,7 and 14 days after curcumin injection(T1-5).The rats were sacrificed after MWT and TWL were measured at T3-5,and the lumbar segments of the spinal cord and DRG (L4-6) were removed for determination of the expression of MMP-2 and MMP-9 by Western blot.Results Compared with group C,MWT was significantly decreased and TWL was shortened,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was up-regulated in DNP,Cur and SC groups.Compared with DNP group,MWT was significantly increased and TWL was prolonged,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was down-regulated in Cur group,and no significant changes were found in the parameters mentioned above in SC group.Conclusion The mechanism by which curcumin attenuates type 2 DNP may be related to up-regulation of the expression of MMP-2 and MMP-9 in the spinal dorsal horns and DRG of rats.
ABSTRACT
Objective To evaluate the effects of curcumin on the expression of receptor for advanced glycation end-products (RAGE) in the spinal dorsal horn and dorsal root ganglion (DRG) of the rats with type 2 diabetic neuropathic pain (DNP).Methods Male Sprague-Dawley rats,weighing 160-180 g,were used in this study.Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet for 8 weeks and intraperitoneal streptozotocin (STZ) 35 mg/kg and confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later.Type 2 DNPwas confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after STZ administration less than 80％ of the baseline value.Eighty-one rats with type 2 DNP were randomly divided into 3 groups (n =27 each) using a random number table:DNP group,DNP + curcumin group (DCur group),and DNP+ solvent group (group DSC).In DCur and DSC groups,curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml · kg-1 · d-1 were injected intraperitonally,respectively,for 14 consecutive days starting from the day 14 after STZ administration.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before STZ injection,at day 14 after STZ injection,and on 3,7 and 14 days after curcumin injection.RAGE positive cells were determined by immuno-histochemistry and the expression of RAGE by Western blot in the spinal dorsal horn and DRG after MWT and TWL were measured on 3,7 and 14 days after curcumin injection.Results Compared with group C,MWT was significantly decreased and TWL was shortened at 14 days after STZ injection and each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was increased at each time point after curcumin injection,and the expression of RAGE was up-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DNP.Compared with group DNP,MWT was significantly increased and TWL was prolonged at each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was significantly decreased at 7 and 14 days after curcumin injection,and the expression of RAGE was down-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DCur,and no significant change was found in the parameters mentioned above in group DSC.Conclusion The mechanism by which curcumin attenuates DNP may be related to inhibition of up-regulated expression of RAGE in the spinal dorsal horn and DRG of rats with type 2 diabetes mellitus.
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.