Study Of Brain Functional And Structural Changes In Patients With Postherpetic Neuralgia Based On Resting-state Functional Magnetic Resonance Imaging

Background and Objective:Postherpetic neuralgia(PHN)which is defined as typical chronic neuropathic pain syndrome that develops after healed herpes zoster infection and persists for >3months,significantly impacts patient quality of life.With the advent of China's aging population,more and more PHN patients are bound to cause huge medical expenses and economic burden,but the pathogenesis of PHN is complicated,and the existing clinical treatment methods are not effective in treating the disease.Research on its pathogenesis is particularly important.Previous studies have shown that PHN has peripheral nerve injury mechanisms.However,there are few studies on central nervous system changes caused by PHN.PHN can exist with various neuropathic signs that are associated with irreparable damage to the peripheral nervous system.Recently,several neuroimaging studies have explored possible alterations of structure and functions in patients with PHN painChronic pain is a kind of brain dysfunction disease.The formation of pain is related to the network activities of multiple brain regions.It is a complex dynamic process completed by a large number of neurons.It affects the function and behavior in brain by changing the flow and integration of information.,as well as cause a series of functional and structural changes in the nervous system,leading to the persistence of chronic pain and clinical treatment difficulties.In recent years,with the rapid development of functional magnetic resonance imaging(fMRI)technology,it has become a common research for the occurrence and development of neuropathic pain by virtue of its accurate positioning of brain functional regions and non-invasive.fMRI is a useful method to further understand the process of pain formation and management in the central nervous system.Several studies have shown that many regions activated in PHN brain,including insula,thalamus,anterior cingulate gyrus,striatum,hippocampus,amygdala,sacral forehead,… These brain regions associated with emotion,affective processes,hedonics,and reward.In addition,recent studies also shown that patients with PHN have extensive brain gray matter abnormalities,which also reflects the structural damage in PHN brain.At present,the changes of functional and structural in specific regions in PHN patients are still unclear,so it is necessary to conduct in-depth research on brain function and structural changes in PHN patients.This study was based on the fMRI technique to analyze the functional and structural changes in the brain regions of PHN patients and their relationship with clinical assessment scales to further explore the central pathogenesis of PHN.Therefore,the main purposes of this study include:1.Using the resting state functional magnetic resonance imaging(rs-fMRI)technique to compare the differences in brain homotopy functional connections between the PHN group and the normal control group based on the voxel-mirrored homotopic connectivity(VMHC)method.As well as to explore interhemispheric intrinsic connectivity in PHN patients.2.Using the low frequency amplitude(ALFF)method to study the spontaneous low frequency amplitude activity of brain neurons in PHN patients,and to explore the changes of ALFF values in different frequency bands(slow-4;slow-5;typical frequency bands),and the Correlation between the ALFF values of altered regions and clinical parameters.3.Using Voxel-based morphometry(VBM)method to objectively evaluate brain gray matter abnormalities,further to analyze potential gray matter volume changes in patients with PHN.Methods:1.18 cases of right-handed PHN patients and 18 well-matched healthy control subjects were collected.VMHC method was used to analyze rs-fMRI data of all subjects,and the correlation between VMHC values and clinical parameters in relevant brain regions was analyzed.2.3.0TMRI scan were performed in 18 PHN patients and matched with gender,age and education level healthy controls.ALFF analysis was performed using REST software to calculate the low-frequency oscillation amplitude of the image signal in the slow-4 band(0.027-0.073Hz),slow-5 band(0.01-0.027Hz),and typical band(0.01-0.08Hz)reflecting the gray matter signal.And calculate the average value of ALFF,and then use SPM8 to statistically analyze the obtained ALFF value,and further analyze the correlation between the ALFF value of the differential brain region and the clinical scale.3.22 PHN patients and 22 healthy controls matched with age,gender and education level were collected.The changes of gray matter volume in the two groups were compared by VBM method,and the correlation between the alterations of gray matter volume and VAS and course of disease in PHN patients were analyzed.Results:1.Compared with the healthy controls,the patients with PHN showed abnorm-ally decreased homotopic connectivity in the dorsolateral prefrontal cortex and the precuneus and posterior cingulate cortex(PCUN/PCC).The decreased VMHC in the PCUN/PCC was positively correlated with the visual analog scale of PHN in the PHN patient group(r=0.651;P=0.006).Receiver operating characteristic(ROC)analysis revealed that the areas under the curves for the two brain regions were 0.898 for the prefrontal cortex and 0.923 for the PCUN/PCC,which indicated that the VMHC could be used to discriminate PHN patients from healthy controls.2.The ALFF results revealed significantly higher ALFF values in the typical frequency band.Ccompared with HCs,PHN patients showed prominently decreased ALFF in the right prefrontal cortex(PFC)and increased ALFF in the bilateral brainstem/cerebellum anterior lobe(BS/CAL).Brain regions with a main effect of group included significantly increased ALFF(PHN>HCs)regions in the BS/CAL,the left precuneus/superior middle temporal gyrus(PCUN/sMTG),and the right precuneus(PCUN)and significantly decreased ALFF(PHN<HCs)regions in the right cerebellum posterior lobe(CPL),the right PFC,the left PFC,and the right supplementary motor area/M1(SMA/M1).While,in main effect of frequency band,increased ALFF(slow-5>slow-4)in the right medial frontal gyrus(MFG),the left MFG,the bilateral BS/CAL and a significantly decreased ALFF(slow-5 < slow-4)in the right BS,the bilateral midcingulate cortex(MCC),and the right insular/superior temporal gyrus(Ins/STG).There were no significant interactions between different groups and frequency bands.Further post hoc t-tests showed bidirectional changes inALFF across slow-4 and slow-5 frequencies between the PHN and HC groups.Significantly decreased ALFF values were identified in the bilateral cuneus/lingual gyrus and the right PFC in the slow-4 band,but significantly increased ALFF values were identified in the bilateral BS/CAL and the left parieto-occipital cortex(POC)in the slow-5 band.3.Compared with the HC group,PHN patients showed decreased GMV in the left insula lobe,right middle frontal gyrus(MFG),right insula lobe,left precentral gyrus,right precentral gyrus,and left postcentral gyrus,while Significantly increased GMV in the left cerebellar posterior lobe(CPL),right parahippocampal gyrus,and right lentiform nucleus.In the PHN brain,the GMV changes in the left CPL and right hippocampus were positively correlated with VAS scores.The change in GMV in the left insula was negatively correlated with the duration of pain.The GMV of the left precentral gyrus and left postcentral gyrus showed significant negative correlations with VAS scores in PHN subjects.Conclusion:1.Our results indicated reduced interhemispheric functional connectivity in patients with PHN,which seems to be an important new avenue to investigate to better understand the nature of disconnection of the functional architecture in patients with PHN.2.Our results suggested that the intrinsic brain activity of PHN patients was abnormal and frequency dependent,especially the bidirectional alteration in ALFF across the slow-4 and slow-5 frequencies in the brains of PHN patients.These findings illuminate alterations in PHN-related frequency-dependent changes in ALFF and provide new insights into the pathophysiology of PHN.3.Our results showed larger GMV alterations in PHN brains,which indicate the complexity of the central mechanism.PHN is not only connected with pain-related regions but also with regions related to emotion,memory,and behavior.