| Objective:To explore the role of PKCεand intervention study of gabapentin in the mechanism ofcentral sensitization of migraine.Methods:144healthy adult male SD rats, weighting from200to250g, were randomly dividedinto seven groups: Normal group(N group), sham operation group(C group), Migrainemodel group(M group), Flunarizine group(F group), Gabapentin group(G group), and H-7group, with24rats in each group. Then the experiment was carried out in the respects ofdural blood flow, discharge frequency in the extracellular spinal trigeminal nucleus, PKCεmembrane translocation and the content of amino acids in cerebrospinal fluid through thetechnique of electrophysiology, Western-blot and liquid chromatography-massspectrometry. All experimental data were presented as mean±standard deviation（x±S）,statistical test was processed by SPSS10.0software package one way ANOVA, significantlevel was P<0.05.Results:This experiment copied the model of Moskowitz migraine in the rats. After the modelis duplicated, the rats showed the behavioral changes in the form of stimulation in lateralmasticatory muscle contraction, increased in oral and nasal secretions, frequentlyscratching heads of the forelimbs, closed eyes, increased frequency of climbing cage anddysphoria.(1)The test of dural blood flow:2hours after making model, compared withcontrol group, the dural blood flow in model group increased obviously, the statisticsshowed significant difference, P<0.01; compared with model group, the dural blood flowin Flunarizine group, Gabapentin group and H-7group decreased obviously, P<0.01;Compared with Flunarizine group, the dural blood flow decreased obviously in Gabapentingroup and H-7group respectively, P<0.01; compared with Gabapentin group, H-7group decreased obviously, P<0.01; compared with control group, the blood flow increasedobviously, P<0.01; compared with control group, blood flow showed no significantdifference in Gabapentin group, P>0.05; compared with control group, blood flowdecreased obviously in H-7group, P<0.01.(2) The monitor of discharge frequency in theextracellular spinal trigeminal nucleus: after making model of migraine in the rats,discharge frequency in the extracellular spinal trigeminal nucleus increased,2hours aftermaking model, the frequency is325.88±47.32%before making model; compared with H-7group and model group, the discharge frequency decreased obviously in Flunarizine groupand Gabapentin group, P<0.01; compared with control group, discharge frequency inFlunarizine group and Gabapentin group increased, P<0.01; compared with control group,discharge frequency in H-7group had no obvious change, P>0.05; compared withFlunarizine group, discharge frequency in Gabapentin group and H-7group decreasedobviously, P<0.01; there was no significant difference between H-7group andGabapentin group, P>0.05.(3) The test of PKCεmembrane translocation: compared withGabapentin group and control group, PKCεmembrane translocation in model group andFlunarizine group increased obviously, P<0.01; compared with control group, H-7groupdecreased obviously, P<0.01; compared with H-7group and model group, Flunarizinegroup and Gabapentin group decreased obviously, P<0.01; there was no significantdifference between Gabapentin group and Flunarizine group, P>0.05; compared withFlunarizine group, H-7group decreased obviously, P<0.01; compared with Gabapentingroup, H-7group decreased obviously, P<0.01.(4) The determination of content of aminoacids in cerebrospinal fluid: Compared with normal group, the content of excitatory aminoacids(glutamic acid, aspartic acid) increased in model group, Flunarizine group andGabapentin group, P<0.01; compared with control group, there was no significantdifference in H-7group, P>0.05; compared with model group, the contents of excitatoryamino acids in Flunarizine group, Gabapentin group and H-7group decreased obviously,P<0.01; compared with Flunarizine group, Gabapentin group and H-7group decreasedobviously, P<0.01or P<0.05; compared with Gabapentin group, H-7group also decreased,P<0.01; compared with normal group, the contents of inhibitory amino acids(γ-aminobutyric acid and serine) in model group, Flunarizine group and Gabapentin groupdecreased obviously, P<0.01; compared with H-7group, there was no obvious difference inmodel group, Flunarizine group and Gabapentin group, P>0.05.Conclusions:(1) PKCεparticipates in the mechanism of migraine central sensitization, and it can be used as potential drug for the treatment of migraine central sensitization;(2)Flunarizine, gabapentin and H-7play part in the treatment of migraine central sensitization,in which gabapentin is better than flunarizine, H-7is better than gabapentin.Innovations:1. Explore the mechanism of migraine central sensitization in a preliminary way.Prove that PKCε plays an important part in the development of migraine centralsensitization.2. Starting from the point of the mechanism of migraine central sensitization,potential drug for the treatment of migraine is studied. It proves that the inhibitors, suchas flunarizine, gabapentin and H-7play part in the treatment of migraine centralsensitization.3. Study the different efficacies of drugs on the treatment of migraine centralsensitization. It proves that gabapentin is better than flunarizine while H-7is better thangabapentin. |
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