Structural Reorganization of Hypothalamic Subfields in Postherpetic Neuralgia: Volumetric and Morphometric Covariance Network Analyses

Abstract

Background

Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition associated with central nervous system reorganization, but hypothalamic alterations remain poorly understood. We investigated hypothalamic subfield volumes and morphometric covariance network organization in patients with PHN.

Methods

This prospective cross-sectional study included 42 patients with PHN and 41 healthy controls whose hypothalamic subfield volumes were obtained from T1-weighted MRI using automated FreeSurfer segmentation. Bilateral mean raw subfield volumes were compared between groups using analysis of covariance, adjusting for age, sex and estimated total intracranial volume, with false discovery rate correction for multiple comparisons. Morphometric covariance networks were constructed from age- and sex-residualized subfield volumes and graph-theoretical measures were compared using permutation testing.

Results

After adjustment for estimated total intracranial volume, age and sex, the tubular superior subfield was nominally larger in PHN (adjusted difference, 4.95 mm³; 95% CI, 0.05–9.85; p = 0.048), but did not survive FDR correction. No other subfield or whole-hypothalamic volume differed significantly. PHN showed reduced local efficiency and clustering coefficient and increased characteristic path length, without a significant difference in global efficiency. No pain-side-dependent lateralization or significant associations between subfield volumes and pain measures or disease duration were observed.

Conclusions

PHN was associated with altered hypothalamic morphometric covariance organization, characterized by reduced local network segregation and increased characteristic path length, while regional volume differences were limited after intracranial volume correction. These findings suggest that PHN-related central reorganization may involve hypothalamic systems related to homeostatic regulation and stress adaptation.

Significance Statement

This study demonstrates altered morphometric covariance organization of hypothalamic subfields in postherpetic neuralgia, despite limited evidence of regional volumetric differences after intracranial volume adjustment. These findings suggest that hypothalamic involvement in PHN may be better reflected by altered coordinated structural organization than by regional volume changes alone.