Analysis Of Central Sensitization Related Factors And Changes Of Glutamate In Cingulate Cortex In Migraine Patients

Background:Migraine is a common and recurrent primary headache.Its clinical symptoms are unilateral or bilateral throbbing headache,which can be combined with nausea,vomiting,photophobia,phonophobia,worsening after activities and other characteristics.At present,no consensus has been reached on its pathogenesis.The imbalance of excitatory and inhibitory neurotransmitters leads to the increase of cortical excitability and central sensitization,which is one of the most evidential theories in the pathophysiological mechanism.Glutamate,one of the most important excitatory neurotransmitters in the Central Nervous System(CNS),has been found to change significantly in various body fluids,including cerebrospinal fluid,blood platelets,in patients with migraine.With the development of magnetic resonance spectrum(MRS),it is possible to directly measure the level of intracranial metabolites.The central sensitization symptoms of migraine patients,including cutaneous allodynia(CA)and hyperalgesia,are particularly prominent.Many studies have found that glutamate plays an important role in the occurrence of migraine central sensitization.In this study,MRS was used to quantitatively detect glutamate levels in the anterior and posterior cingulate cortex(ACC and PCC)of migraine patients and age-matched healthy controls,respectively in the paroxysmal phase and interparoxysmal phase.To contrast the differences of glutamate levels between migraine patients during the paroxysmal phase and interparoxysmal phase and between patients and healthy controls.At the same time,the central sensitization symptoms of the patients were quantified and the correlation between them and the level of glutamate was analyzed.This study contains three parts,as follows:Part 1.Analysis of related factors of central sensitization in patients with migraineObjective:To explore the relationship between central sensitization symptoms and other clinical features and comorbidities in migraine patients.Materials and methods:Sixty patients with migraine who were treated in the Headache Clinic of Department of Neurology,Shandong Provincial Hospital and fourteen matched controls were recruited in the research between November 2020 and January 2021.Filling out the Allodynia Symptom Checklist(ASC)to evaluate central sensitization symptoms.The basic clinical characteristics of migraine,such as frequency of attack and duration of attack,HIT-6,MIDAS,PHQ-9,GAD-7,non-headache symptom questionnaire and pain catastrophization scale were completed.Two-sample t test was used to verify the relationship between central sensitization symptoms and comorbidity and other clinical characteristics.Results:A total of 60 migraine patients(51 female,9 male,age 20-47 years old,average age 29.83±6.79 years old)completed the questionnaire,among which 47 patients(43 female,7 male,age 20-47 years old,average age 30.28±7.10 years old)had CA,accounting for 78.33%.There were 13 cases without CA(11 cases were female,2 cases were male,age 21-40 years old,average age 28.23±5.24 years old),accounting for 21.67%.Compared without CA patients with migraine,migraine patients with CA in the course of longer,attack frequency is higher,attacks last longer,the severity of the headache is higher,the impact on the life more serious.In the non-headache symptom and pain catastrophization scale,there were no significant differences between them.The migraine patients with CA have a higher probability of anxiety and depression comorbidity.Conclusion:Compared with migraine patients without CA,migraine patients with CA have a longer course of disease,a higher frequency of attack,a longer duration of attack,a higher degree of headache severity,a more serious impact on life,and a higher incidence of co-morbidity with anxiety and depression.There is no significant difference in non-headache symptoms and pain catastrophization scores.Part 2.Alteration of brain glutamate levels in patients with migraineObjective:Using MRS to quantitatively detect glutamate levels in the anterior and posterior cingulate cortex(ACC and PCC)of migraine patients and age-matched healthy controls,respectively in the paroxysmal phase and interparoxysmal phase.To contrast the differences of glutamate levels between migraine patients during the paroxysmal phase and interparoxysmal phase and between patients and healthy controls.Materials and methods:Twenty-one patients with migraine(26.40±3.03y)who were treated in the Headache Clinic of Department of Neurology,Shandong Provincial Hospital and fourteen matched controls(26.70±2.52y)were recruited in the research between November 2020 and January 2021.The volume of interest(VOI)was placed respectively in the corresponding anterior cingulate cortex/medial prefrontal cortex(ACC/MPFC)and the posterior cingulate cortex(PCC)on the 3D T1WI reconstruction image by using Philips 3.0T Iningenia CX MR imager.Glutamate spectrum data were collected by Point-resolved spectroscopy from patients during the paroxysmal phase as well as interparoxysmal phase and healthy controls.Tarquin(version 4.3.10)was used for data post-processing.Results:In the anterior and posterior cingulate cortex,there was no statistically significant difference in the level of glutamate in the same patient during the paroxysmal phase and the interparoxysmal phase.There was no significant difference in the level of glutamate between the migraine group and the control group.Conclusion:There was no significant difference in the levels of glutamate in the cingulate cortex of migraine patients during the paroxysmal phase and the interparoxysmal phase,between migraine patients and healthy controls.Part 3.Correlation between glutamate levels in brain and central sensitization in migraine patientsObjective:To explore the correlation between the levels of glutamate in anterior and posterior cingulate gyrus and central sensitization symptoms in patients with migraine.Materials and methods:Thirty-five patients with migraine(29.94±7.99y)who were treated in the Headache Clinic of Department of Neurology,Shandong Provincial Hospital were recruited in the research between November 2020 and January 2021.The mechanical tenderness threshold of patients was recorded,and the Allodynia Symptom Checklist(ASC)was filled out.Pearson correlation analysis was used to verify the correlation between quantified central sensitization symptoms and glutamate levels in anterior and posterior cingulate gyrus obtained by MRS.Results:A total of 35 migraine patients completed the ASC,including 8 males(22.9%)and 27 females(77.1%),aged 21-55 years(mean 29.94±7.99),and 18 migraine patients with CA.There was linear correlation between the level of glutamate in the anterior cingulate gyrus and the mechanical tenderness threshold during attack.Conclusion:CA was present in 51%of migraine patients.There was linear correlation between the level of glutamate in the anterior cingulate gyrus and the mechanical tenderness threshold during attack.