Cortical reorganization in neuropathic pain due to peripheral nerve degeneration: altered cortical surface morphometry and hierarchical topography

Abstract Degeneration of peripheral nerves causes neuropathic pain. Previous studies have documented structural and functional brain alterations in peripheral neuropathy, which may be attributed to maladaptive plasticity following chronic neuropathic pain. Nevertheless, the effects of peripheral neuropathic pain on the macroscale organization of the cerebral cortex have not been explored. This study investigated altered surface morphology and topographic hierarchy of the cerebral cortex in patients with neuropathic pain due to peripheral neuropathy. T1-weighted magnetic resonance imaging data were acquired from 52 patients with peripheral neuropathic pain and 50 age- and sex-matched healthy controls. Cortical morphometric features including thickness and gyrification index were obtained using surface-based morphometry. A topographic gradient encoding interregional similarity in cortical thickness was extracted using a machine-learning technique named diffusion map embedding. Compared with controls, patients with neuropathic pain exhibited cortical thinning in the frontal and sensorimotor cortices, with the severity increasing with greater neuropathic pain. The patients also showed decreased gyrification in the insula, with a greater reduction in gyrification linked to more severe skin nerve degeneration. Moreover, the patients exhibited altered topographic organization of the cerebral cortex, where the direction of the topographic gradient deviated from the occipital-to-frontal axis observed in the controls in this study and reported in the literature. Our findings provided a novel perspective for macroscale cortical structural reorganization after neuropathic pain, showing thinning and gyral flattening in pain-related areas and deviation from the normal topographic axis of the cerebral cortex.