Effect Of RTMS On Major Depressive Disorder With Pain Symptoms And Its Functional Magnetic Resonance Imaging

Objective:Major depressive disorder(MDD)is a common mental disorder characterized by persistent and significant depressed mood,often associated with physical pain symptoms(PPS),which may lead to poor efficacy of MDD,and the relevant mechanisms are not yet fully understood.Studies have shown that MDD with physical pain has its related brain network characteristics,our study mainly aims to observe the clinical therapeutic effect of rTMS on MDD patients with physical pain and the regulation of related brain networks,and discuss the clinical treatment and mechanism of MDD with pain.Methods:Patients with first-episode MDD who visited the outpatient clinic of our neurology and mental health center from January 2021 to January 2022 were collected.A total of 30 first-episode MDD patients without medication were included,including 14 patients with pain(MDD pain group)and 16 patients without pain(MDD pain-free group).They were treated with 10 Hz left dorsolateral prefrontal cortex(DLPFC)rTMS for 2 weeks(5 times a week,10 times in total,3000 pulses each time),and Hamilton Depression Rating Scale-17(HAMD-17)and pain VAS score were performed before and after treatment to assess depression and pain symptoms.Before and after treatment,contact heat stimulation(CHS)was used to give pain stimulation,and task-state fMRI was performed at the same time.MATLAB2018b and SPM12 software were used to analyze task-state fMRI image data to observe the differences in brain activation before and after rTMS treatment in MDD with pain.General clinical data and scale scores were analyzed using SPSS 23.0 software.Results:There was no statistically significant in age,gender,course of disease,years of education between MDD pain group and MDD pain-free group patients(P>0.05).There was no significant difference in HAMD-17 score at baseline among all patients.After 2 weeks of rTMS treatment,the depressive symptoms of the two groups were improved(P<0.001).There was significant difference in VAS score between MDD pain group and MDD pain-free group.After rTMS treatment,the pain symptoms were significantly relieved in MDD pain group compared with those before treatment(P<0.001).Task-state CHS-fMRI results showed that brain regions activated more strongly in the MDD pain group than in the MDD pain-free group at baseline included right rolandic operculum,right insula,right inferior temporal gyrus,right superior temporal gyrus,right fusiform gyrus,and right cerebellar region 8(P<0.005,uncorrected).After rTMS treatment,the brain regions with weaker activation in the MDD pain group than in the MDD pain-free group included right inferior temporal gyrus,right insula,right fusiform gyrus,right cerebellar region 6,and left cerebellar region 4-5.The decreased activation of brain regions after rTMS treatment in MDD pain group included bilateral cerebellum,right rolandic operculum,right inferior temporal gyrus,right superior temporal gyrus,right fusiform gyrus,and right insula.While the activation of the above brain regions was enhanced after treatment in the MDD pain-free group.Pearson correlation analysis of HAMD-17 and VAS scales and brain regions activation in the two groups revealed that there was a correlation between the right inferior temporal gyrus and the pain VAS score in the MDD pain group,and there was a negative correlation before treatment(R=-0.872,P=0.002)and after treatment(R=-0.913,P=0.001).However,no correlation was found between other clinical scales and brain regions activation.Only some of the patients in both groups had transient mild scalp pain or dizziness during rTMS treatment.Conclusion:1.High-frequency rTMS treatment of the left DLPFC can significantly improve depression and physical pain symptoms in MDD patients with pain.2.rTMS has a regulatory effect on pain-related brain networks in MDD with pain.Physical pain symptoms in MDD patients may be related to increased brain activation regions of the right insula,right rolandic operculum,right superior temporal gyrus and fusiform gyrus,and their degree of activation was decreased after rTMS treatment compared with that before treatment.rTMS may improve pain symptoms by repairing the pain brain networks related to the right insula,right rolandic operculum,right superior temporal gyrus and fusiform gyrus.3.rTMS has a good safety for the treatment of MDD patients with pain.