ABSTRACT
Objective To evaluate the effect of B-vitamins(B1,B6,B12)on diabetic neuropathic pain (DNP)in rats.Methods 104 male SD rals weighing 200-230 g were randomly divided into 13 groups(n=8 each):group Ⅰ control(group C);group Ⅱ DNP;group Ⅲ DNP+ normal saline(solvent of vitamins,group NS);group Ⅳ,Ⅴ,Ⅵ DNP+vitamin B1 10,33 or 100mg/kg,kg(group B1 10,group B133,group B1 100);group Ⅶ,Ⅷ,Ⅺ DNP+vitamin B6 10,33 or 100 mg/kg(group B6 10,group B633,group B6100);group Ⅹ,Ⅲ,ⅫDNP+vitamin B12 0.5,1.5 or 4.5 mg/kg (group B12 0.5,group B121.5,group B124.5)and group ⅩⅢ DNP+vitamin B1 10/B6 33/B12 1.5 mg/kg(group VBC).Diabetes was induced with intraperitoneal(IP) streptozocin mg/kg in group Ⅱ-ⅩⅢ.B-vitamins were give.IP once a day for 14 consecutive days starting from 14 d after IP streptozocin in group Ⅳ-ⅩⅢ.Venous blood samples were taken before(baseline)and 3 d after IP streptozocin for determination of blood glucose level. Successful induction of diabetes was defined as blood glucose > 14.6 mmol/L. Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured 2 days before and 14 days after IP streptozocin and on the 1, 3, 7, 14 days of B-vitamin administration. Animals with pain threshold measured at 14 days after IP streptozocin decreasing by less than 15% of the baseline were excluded from the study. The animals were sacrificed after the last pain threshold measurement and L4,5 lumbar segment of the spinal cord and dorsal root ganglions (DRG) were removed for determination of p-CREB expression using immuno-histuchemistry. Results MWT was significantly lower and TWL was significantly shorter and the expression of p-CREB was significantly higher in the other groups than in group C. B-vitamin administration significantly reduced thermal and mechanical hyperalgesia induced by diabetes and down-regulated the expression of p-CREB in a dose-dependent manner as compared with group DNP. The inhibitory effect of vitamin B complex against thermal and mechanical hyperalgesia was significantly stronger and the expression of p-CREB was significantly lower in group VBC as compared with group B110, group B633 and group B121 .5 respectively. Conclusion B-vitamains can attenuate DNP through inhibition of phospberylation of CREB in the spinal dorsal horn and DRG.
ABSTRACT
Objective To evaluate the effect of curcumin on diabetic neuropathic pain (DNP) in rats. Methods Forty-eight male SD rats weighing 200-230 g were randomly divided into 6 groups ( n = 8 each) : group Ⅰ normal control (group C); group Ⅱ DNP (group D) ; group Ⅲ DNP+ DMSO (solvent of curcumin) (group DD) and group Ⅳ , Ⅴ , Ⅵ DNP + curcumin 50, 100 or 200 mg/kg ( group DC50, 100, 200 ). Diabetes was induced with intraperitoneal (IP) streptozocin 75 mg/kg in group Ⅱ -Ⅵ. Curcumin 50, 100 and 200 mg/kg were given IP once a day for 14 consecutive days starting from 14 d after streptozocin in group Ⅳ , Ⅴ and Ⅵ respectively. Venous blood samples were taken before and 72 h after IP streptosocin for determination of blood glucose level. Successful induction of diabetes was defined as blood glucose > 14.6 mmol/L. Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured 2 d before and 14 d after IP streptesocin and on the 1, 3, 7, 14 d of curcumin administration. Animals with pain threshold measured at 14 d after IP streptozocin decreasing by less than 15% of the baseline were excluded from the study. The animals were sacrificed after the last pain threshold measurement and the lumbar segment of the spinal cord and p65 was significantly higher in group D than in group C ( P < 0.05). Curcumin administration significantly reduced thermal and mechanical hyperalgesia induced by diabetes and down-regulated the expression of p-JNK and horn and DRG.