Role of nitric oxide in spinal cord in maintenance of diabetic neuropathic pain in rats

Abstract

Objective To evaluate the role of nitric oxide (NO) in the spinal cord in the maintenance of diabetic neuropathic pain in rats.Methods Male Sprague-Dawley rats,aged 2 months,weighing 180-200 g,were used in the study.Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L on day 2 after STZ injection.Twenty diabetic rats were randomly allocated into diabetes mellitus group (DM group,n =10) and L-NAME (non-selective NOS inhibitor) group (LN group,n =10).Another 10 age-matched normal rats served as control group (C group).On 21 days after STZ injection,L-NAME 10 mg/kg was injected intraperitoneally once a day for 7 consecutive days in LN group,whereas the equal volume of normal saline 5 ml/kg was given instead of L-NAME in DM group.Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before STZ infection and on 7,14,21 and28 days after STZ injection.The rats were sacrificed after the last measurement of PWT and the lumbar segments of spinal cord were removed for determination of NO content and neuronal nitric oxide synthase (nNOS) expression (by Western blot analysis) in spinal cord tissues.Results Compared with C group,PWT was significantly decreased on 14,21 and 28 days after STZ injection,and the NO content and nNOS expression in spinal cord tissues were increased in DM and LN groups (P ＜ 0.05).Compared with DM group,PWT was significantly increased on 28 days after STZ injection,and the NO content and nNOS expression in spinal cord tissues were decreased in LN group (P ＜ 0.05).Conclusion NO in the spinal cord is involved in the maintenance of diabetic neuropathic pain in rats and the mechanism is related to the enhanced function of nNOS. Key words: Nitric oxide ; Spinal cord ; Diabetes mellitus ; Neuralgia