Research Pramipexole On The Regulation Of Dopamine D2 Receptors In Parkinson’s Pathological Pain

Parkinson’s disease(PD),as a neurodegenerative disease,is mainly manifested in two categories: Motor1symptoms(MS)and Non-motor1symptoms(NMS),among which pain,as one of the main factors affecting patients,has a serious impact on patients’ lives.The main pathological feature of Parkinson’s disease is the degeneration and death of dopaminergic neurons in Substantia1nigra(SN)in the midbrain,which causes changes in the content and function of dopamine receptor subtypes in striatum neurons.Dopamine D2 receptor(DRD2)is involved in regulating various symptoms of patients with Parkinson’s disease,but the mechanism of DRD2 in Parkinson’s pathological pain is not clear.Therefore,we use Pramipexole(PPX),an agonist of DRD2,to explore the regulation mechanism of DRD2 in Parkinson’s pathological pain,so as to provide theoretical and practical basis for the study of dopamine receptor in Parkinson’s pathological pain,and provide direction and theoretical support for the prevention and intervention of Parkinson’s pathological pain.The main results are as follows:1.Dopamine receptor agonist pramipexole can improve the movement of Parkinson’s disease model mice.Two weeks after modeling,the results of stick-rotating experiment showed that the stick-holding time of Parkinson’s disease model mice was significantly shorter than that of normal mice(P<0.001),which suggested that the model of Parkinson’s disease was successful.one The results of behavioral experiments,such as open field,Frye’s hair pain measurement and hot stabbing pain,showed that the pain tolerance value of Parkinson’s disease model mice began to decline,and was significantly lower than that of normal mice(P<0.001).Through detection and analysis,it can be known that the motor ability of Parkinson’s disease model mice has decreased compared with normal mice after modeling,and the pain threshold of Parkinson’s disease model mice has decreased when receiving pain test,which shows that pramipexole can effectively treat Parkinson’s pathological pain.2.pramipexole can improve the pain threshold of Parkinson’s disease model mice.It is verified by experiments that pramipexole can effectively improve the pathological pain of Parkinson’s disease,but the improvement degree of different degrees of pramipexole is different.The experimental results show that the middle dose(1m1/kg)of pramipexole has a better therapeutic effect on the pain(P<0.001),followed by the high dose(3 mg/kg),and the low dose(0.5 mg/kg)may be due to.3.The expression of DRD2,apoptosis-related factors Bcl-2,Bax and Caspase-3m RNA in striatum and substantia nigra by pramipexole.The results of fluorescence quantitative PCR showed that pramipexole,a dopamine receptor agonist,could improve the pain behavior of Parkinson’s disease model mice through DRD2 pathway.After the model was established,the contents of apoptosis-related factors Bcl-2,Bax and Caspase-3 were all changed due to the existence of apoptosis in mice with Parkinson’s disease.Compared with normal mice,the apoptosis-related factors Bcl-2 were significantly decreased(P<0.05),while the contents of Bcl-2 and Bax in tissues were significantly increased(P<0.05).After treatment with dopamine receptor agonist,apoptosis-related factors can be improved,thus preventing apoptosis in mice.4.THe expression of DRD2 and TH proteins in striatum and substantia nigra of mice.After the determination of protein expression,it was concluded that the relative expression content of DRD2 protein in striatum and substantia nigra of Parkinson’s disease model mice would change after modeling,but the relative expression content of DRD2 protein in substantia nigra of Parkinson’s disease model mice could be significantly reduced(P<0.001)after drug treatment.It can be seen from the experimental results that the relative expression of TH receptor protein in substantia nigra of Parkinson’s disease model mice will change after modeling,and the relative expression of TH receptor protein in substantia nigra of Parkinson’s disease model mice can also be significantly reduced(P<0.001)after drug treatment.To sum up,pramipexole,a dopamine receptor agonist,can improve the pathological pain of Parkinson’s disease through DRD2 pathway,and improve the apoptosis-related factors in tissues,thus alleviating the pathological pain of Parkinson’s disease patients.