Abstract
Objective To evaluate the role played by NMDA receptor (NR1) in spinal cord in diabetic neuropathic pain (DNP) in rats.Methods One hundred and twenty-eight female Wistar rats 3 months old weighing 180-220 g were randomly divided into 4 groups : group Ⅰ control ( group C) ;group Ⅱ DNP;group Ⅲ SB203580 (selective p38MAPK inhibitor) + DNP and group Ⅳ MK-801 + DNP.Diabetes mellitus was induced by intraperitoneal streptozocin 65 mg/kg.Blood glucose level was measured every week for 4 weeks.Diabetes mellitus was confirmed by blood glucose level ≥ 16.0 mmol/L in the 4th week.Mechanical paw withdrawal threshold (MWT) to yon Frey filament stimulation was measured at the end of the 4th week.Diabetic rats with significant decrease in MWT were used in group Ⅱ ,Ⅲ and Ⅳ.Starting from the 1st week after DNP model had successed,SB203580 1 mg/kg and MK-801 1 mg/kg were injected IP once a day in group Ⅲ and Ⅳ respectively.Eight animals were taken from each group for MWT measurement at the end of the 1st,3rd,5th and 7th week after the model was successfully made respectively.The rats were anesthetized and nerve conduction velocity (NCV) of the left sciatic nerve was measured.The rats were then killed and fight sciatic nerve,the lumbar segment of the spinal cord and dorsal root ganglion (DRG) were removed for microscopic examination and determination of the level of DOI: 10.3760/cma.j.issn.0254-1416.2009.05.010phosphorylated p38 MARK (p-p38MAPK) and the expression of NR1 in the neurons of DRG and spinal cord.Results The MWT and NCV were significantly lower and the p-p38MAPK level and NR1 expression in the spinal cord and DRG were significantly higher in group Ⅱ ,Ⅲ and Ⅳ than in group C at all time points.SB203580 and MK-801 significantly attenuated the diabetes-induced changes in group Ⅲ and Ⅳ respectively.Conclusion Activation of NMDA receptor in spinal cord is involved in the diabetic neuropathic pain. Key words: Receptors,N-methyl-D-aspartate; p38 Mitogen-activated protein kinases; Diabetic neuropathies; Neuralgia
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