Vault Of Heaven Analgesic Capsule Prevention Of Migraine Pharmacodynamic Mechanism

Migraine is a common and complex neurological disorder that often attacks recurrently and is difficult to cure completely. An investigation made by WHO reveals that migraine is one of the chronic disease which seriously influence the quality of the patient's life.It affects a significant proportion of the adult population worldwide.It represents an enormous socio-economic burden to the individual as well as to the socity. Although a great variety western medicine have been prepared,it is short of drugs which have no side effects and have positive prostecdtive efficacy.The effects of Chinese materia medica is mildly and have little side effects.This research aims at applying the theory of TCM combined with the modern scientific medhod to uncover the theory and experience about migraine,discussing the special feature of TCM,providing reference for the clinical usage of Chinese materia medica reasonably,safely and efficiently.1.Study of literatureWe collected considerable literature of migraine from ancient period to present period, and collected clinical reports published in medical magazines in 2000-2007 which treat migraine.Then discussed the special feature about the name,etiopathogenisis,diagnosis and treatment by diferentiation of syndromes of TCM about migraine.The result of analysis is that wind, stagnated blood,and phlegm and deficiency are the primal etiological factor.Wind blocking the meridian, excessive rising of liver,and stagnated blood blocking meridian is the basic pathogenesis.Expelling wind, calm the liver and stop endogenous wind and promote blood circulation to remove meridian obstruction is the main treating method.According to the foundamental theory of TCM,combining the clinical experience of my advisor and the result of analysis,we make up a prescription named of TianQing Zhitong Capsule to treat migraine to aim directly at the common pathogenesis of migraine,which excessive rising of liver-YANG,wind-syndrome resulting from exogenous or endogenous evils,stagnated blood blocking meridian.The prescription is the combination of differential diagnosis of diseases with differential diagnosis of diseases,local characteristic drugs combining with traditional drugs,and make up a prescription-Tianqiong Zhitong Capsule(TQ) to treat migraine.2.Empirical studyOn the basic of searching the newest advancement about migraine, empirical study about Chinese materia medica and complex prescription preventing and cureing migraine,we design the following experiments: 2.1 The basic pharmacodynamic experiments2.1.1 Experimental study of analgesic effect:We apply hot plate test and writhing test to approach the effects of TQ.The results demonstrate TQ can raise the pain threshold of mouse, prolong the latency and decrease the writhing times of the mouse intraperitoneal injected of acetic acid.It suggest that TQ have analgesic effect2.1.2 Experimental study of sedative effect:We observe the effect of TQ on the autonomic activities of the normal mouse in 5 min.The results demonstrate TQ have the inhibitive effect on the central nervous system..It profits to improve crankous emotion of the migraineurs.2.2 Experimental study of mechanism of action2.2.1 Effects on the content of neurotransmitter in the brain:We apply high- performance liquid chromatography(HPLC) detect the content of 5-HT,DA and NE in the brain of injection NTG animal models of migraine.The results discover that TQ can increase content of 5-HTin the brain,but have no effects on the content of DA,NE in the brain.The results suggest that TQ can inhibit the attack of migraine by promote the effect of 5-HT on the vasoconstriction and the modulation of algesia.2.2.2 Effects on the vasoactive substance:We apply method of radioimmunity(RI) to detect the content of CGRP,ET in the blood plasma of hypodermic injection NTG animal models of migraine. The results discover that TQ can decrease the content of CGRP,ET in the blood plasma. The results suggest that TQ can inhibit blood vessel dilatation and plasma protein extravasation and inhibit the neurogenic inflammation to prevent and cure migraine.2.2.3 Effects on algesia thregulatory substance:We apply method of radioimmunity (RI) to detect the content of CGRP,ET andβ-EPin the blood plasma of animal models of migraine stimulated the dural matter near SSS by electrition.The results discover that TQ can decrease the content of CGRP,ET in the blood plasma and increase the content ofβ-EP in the blood plasma. The results suggest that TQ can inhibit the transmition of nociceptive stimulus from primary esthesioneure to CNS.2.2.4 Effects on CGRPmRNA expression,CRLRmRNA expression and RAMP1mRNA expression:We apply method of reverse transcriptase polymerase chain reaction (RT-PCR) to detect CGRPmRNA expression,CRLRmRNA expression and RAMP1mRNA expression in PAG of animal models of migraine stimulated the dural matter near SSS by electrition.The results discover that TQ can decrease CGRPmRNA expression, CRLRmRNA expression and RAMP1mRNA expression.The results suggest that TQ can inhibit the function of CGRP and the compound made up of its receptor and regulate the function of PAG that can inhibit the transmission of nociceptive stimulus. Based on these above results, we speculate that X can modulate the vasoactive substance to influence the vascular function of dilation and contraction,inhibit neurogenic inflammation which can bring about painful stimulation.It can affect the balance of pain-producing substance and pain-relieving substance, modulate the process of nociceptive stimulus is transmited to central nerve system.3.Peculiarity of the researchTianqing Zhitong Capucal is the combination of differential diagnosis of diseases with differential diagnosis of diseases,local characteristic drugs combining with traditional drugs.The model of electrical stimulation of the superior sagittal sinus is a feasible and advanced animal models of migraine.It has been applied to approach the pathophysiological mechanisms of migraine and the therapeutical effect of the western anti-medicine.It have not been to research the mechanisms of Chinese materia medica.Our study apply the model to discuss the effect of Chinese materia medica first time .CGRP is involved in the pathogenesis of migraine the,having effects on neurogenic inflammation and transmition of algesia.CGRP has been the focus of reseach the pathogenesis and treatment of migraine abroad,but little reseach have done about it in domestic field.The scientific investigation of the CGRP and migraine is significant.