| Background and purposeMigraine is a chronic neurovascular disorder, with the major characteristic of paroxysmal, mild or medium, pulsatile headache. The symptom usually lasts for 4 to 72 hours, and it is often associated with nausea and vomiting, which might get worse under the light or noise and get relieved in the quiet environment. The pathogenesis has been a hot topic of research over the past decades, and the hypothesis of pain central sensitization was proposed recently. Researches indicated the'development of central sensitization might be closely related with intracellular signal conduction. Mitogen-activated protein kinase family of JNK1 can regulate intracellular signal conduction by responding to various stimulus, which is considered as an important transmitter in the pathway of intracellular signal conduction. Many evidence suggusted that JNK played a key role in the induction of mitochondria-dependent apoptosis especially after transient ischemic attack. Activated G protein coupled receptor family of PAR2 could induce signal cascade reaction and was involved in the pathogenesis of inflammation, hemostasis, pain and recovery, cellular morphology and movement. Besides, it's highly expressed in the neurologic system. Hydrochloric acid flunarizine capsule had a definitive effect in the treatment of migraine and was considered as front-line regimen to prevent migraine. However, the exact mechnism is still not known. Based on the concept that altered expression of JNK1 and PAR2 was related with migraine susceptibility, Our research investigated the interventional role of flunarizine on the brain stem, trigeminal ganglia and cerebral dura matter in the animal model resulted from nitroglycerin, in order to discuss the pathogenesis of migraine and find new ways to treat this disease.Methods40 SD rats were randomly divided into 4 groups, normal control group, model group, Flunarizine treatment group and Flunarizine prevention group. Rats in the normal control group were injected with 1.04mL/kg of physiological saline, while rats in model group, Flunarizine treatment group and Flunarizine prevention group are injected with 10mg/kg of nitroglycerin to build experimental migraine model. The model group was fed with 1.04mL/kg of distilled water in 30 minutes after modeling. At the same time,1.04 mg/kg of Flunarizine was irrigated into the stomach in 15-20 minutes after modeling of treatment group. Flunarizine prevention group was pre-irrigated with Flunarizine at 1.04 mg/kg/d for one week before building model. The intraabdominal anesthesia was conducted with 3.5ml/kg of chloral hydrate at 10% in 4 hours after modeling, and samples were obtained by perfusion. Relevant experimental data was obtained by immunohistochemical staining. Statistic analyses were performed with the SPSS 13.0. SNK test was used and Value were considered statistically significant at P<0.05.ResultsImmunoreactive positive substances such as JNK1 and PAR2 were found in dura mater, trigeminal ganglia and brainstem zone in the four groups, among which the expression of model group was up-regulated most significantly. There was statistically significant difference when we compared the expression of JNK1 and PAR2 between model group and normal control group(P<0.01), However, there was not statistically significant difference among the normal control group,Flunarizinetreatment group and Flunarizine prevention group (P>0.05).Conclusion1) The animal model of migraine reproducted by subcutaneous injection of nitroglycerin had a high achievement ratio and good repetition as well as great feasibility. A large number of acute migraine models can be reproducted to apply to research of pathogenesis and therapy in a short time.2) The expression of JNK1, PAR2 was up-regulated when migraine attacked and was down-regulated when migraine became relieved in the cerebral dura mater, trigeminal ganglia and brainstem zone, which indicated that JNK1, PAR2 were involved in the pathogenesis of migraine.3) Both of the expression of JNK1 and PAR2 were down-regulated after the intervention of calcium channel blockers, which indicated that migraine could be prevented through decreasing the intermediate molecules in the signal conduction pathway mediated by direct or indirect antagonist.â– ...
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