Structural and Functional Brain Alterations in Postherpetic Neuralgia: A Systematic Review and Voxel-Wise
Yangching Na1,2, Hongyu Mu2, Jiarun Zhang1,2
1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.
Background:
Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition persisting after herpes zoster, often accompanied by emotional and functional impairment. Neuroimaging suggests central nervous system involvement, but reported structural and functional findings remain inconsistent.
Methods:
We conducted a systematic review and voxel-wise coordinate-based meta-analysis using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). PubMed, Embase, Web of Science, CNKI, and WanFang were searched up to December 31, 2025. Eligible studies used whole-brain resting-state fMRI indices (ALFF, fALFF, or ReHo) or structural MRI with voxel-based morphometry (VBM), reporting standard MNI or Talairach coordinates. Random-effects SDM-PSI analyses were performed for PHN versus healthy controls (HC), PHN versus herpes zoster patients (HZ), and PHN pre- versus post-treatment. Sensitivity, heterogeneity, publication bias, and meta-regression analyses were also conducted.
Results:
Twenty-one studies (31 datasets) were included. Compared with HCs, PHN patients showed increased activity in the right cuneus, left putamen, and right anterior thalamic projections, and decreased activity in the right fusiform gyrus. Structural analyses revealed gray-matter reductions in the left Heschl's gyrus, right precentral gyrus, left postcentral gyrus, and left median cingulate/paracingulate cortex. Compared with HZ patients, PHN showed increased activity in bilateral cerebellar Crus II and decreased activity in the right superior parietal gyrus. Pre- versus post-treatment comparisons revealed limited alterations in the left median cingulate/paracingulate gyri and right lingual gyrus. Major clusters remained robust in sensitivity analyses, with low-to-moderate heterogeneity.
Conclusion:
PHN is associated with convergent structural and functional alterations across cross-modal sensory, affective-cognitive, and cortico-basal ganglia networks. These network-level abnormalities may provide candidate neuroimaging biomarkers for characterizing PHN-related disease state and pain chronicization, as well as preliminary treatment-related neuroimaging features reflecting neuroplasticity. They may also guide future mechanism-based interventions, including network-level neuromodulation strategies. Further longitudinal and interventional studies are needed to validate their clinical utility.
