Magnesium effects on behavior and substance P mRNA expression in the midbrain of a rat migraine model

摘要

BACKGROUND:Substance P participates in pain transmission and modulation,suggesting a close association with migraine headaches.The clinical application of magnesium has been effective in treating migraines,and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE:To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model,and to determine the action pathway of migraine treatment using magnesium. DESIGN,TIME AND SETTING:A completely randomized,controlled,animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS:Magnesium sulfate(25%) was supplied by Tianjin Pharmaceutical Jiaozuo,China. Nitroglycerin was provided by Shanxi Kangbao Biological,China.Substance P primer sequence was synthesized by TaKaRa Biotechnology(Dalian),China. METHODS:A total of 36 healthy,adult,Wistar rats were randomly assigned to 6 groups:control, migraine,low- and high-dose magnesium sulfate treated,and low- and high-dose magnesium sulfate control,with 6 rats in each group.Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups.Five minutes following administration,rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate,while those in high-dose groups were injected with 300 mg/kg magnesium sulfate.No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES:At 2 hours after nitroglycerin injection,substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction.At 60-90 minutes after nitroglycerin injection,behavioral changes of pain were analyzed in the experimental rats. RESULTS:The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group(P<0.05).Following magnesium sulfate injection,substance P mRNA expression increased,compared with the migraine and control groups(P<0.05).In the low-and high-dose magnesium sulfate treated groups,pain behavior was remarkably ameliorated, compared with the migraine group(P<0.05),particularly with the high-dose injection(P<0.05). CONCLUSION:Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner,and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.