Effect of Heme Oxygenase-1 on Apoptosis in Spinal Dorsal Horn Neurons and Neuropathic Pain in Diabetic Rats

Objective To investigate the effect of heme oxygenase-1(HO-1) on apoptosis in spinal dorsal horn neurons and neuropathic pain in diabetic rats,and to research the possible relationship between neuropathic pain and the neurons apoptosis.Methods Twenty-four male SPF Wistar rats,weighing 180-220g,were randomly divided into 3 groups(n=8/group):group C(normal group),group B(rats with diabetes mellitus) and group A(rats with diabetes mellitus accepting Hemin treatment).In groups A and B,65mg/kg streptozocin(STZ) was injected intraperitoneally(IP) to induce diabets mellitus.Group C received equal volume of buffered saline instead.Three days later blood glucose concentration was measured.In groups A and B,rats with blood glucose 16.7mmol/L were excluded from the study.Group A were injected Hemin 25μmol/kg q.2d for 6 weeks.The mechanical withdrawal threshold(MWT) of the paw was measured with von Frey filaments before STZ injection and at 1,2,3,4,5 and 6 weeks after STZ injection.Rats were then sacrificed,and the lumbar segments(L4-6) of the spinal cord were removed.Pathologic changes were observed by Nissal's staining under electronic microscope.HO-1 expression was detected by immuno-histochemistry.Apoptosis in the dorsal horn neurons was detected by TdT-mediated dUTP nick end labeling(TUNEL).Results The MWT of group A was increased significantly than group B at 4 weeks after STZ injection(P0.05) and at 5 and 6 weeks after STZ injection(P0.01).The HO-1 expression in group A was significantly higher than that in group B which was higher than in group C.Compared with group B,the histopathological damage to the neurons and the destruction of sciatic nerve myelin sheath was lighter and the apoptotic index was lower in group A.Conclusion HO-1 can reduce neuronal apoptosis in spinal dorsal horn and attenuate neuropathic pain in diabetic rats.Neuropathic pain and the neurons apoptosis have a certain relationship.