Altered patterns in the prefrontal cortex and limbic system in female patients with neuropathic pain secondary to recurrent median nerve entrapment post carpal tunnel release

Brain Commun. 2025 Sep 26;7(6):fcaf375. doi: 10.1093/braincomms/fcaf375. eCollection 2025.

Abstract

Abnormal central pain sensitization is a possible explanation for persistent neuropathic pain after carpal release. However, its exact mechanism remains unclear. This study examined the cortical patterns in chronic neuropathic pain secondary to recurring median neuropathy. Forty-nine patients with recurrent painful carpal tunnel syndrome and 22 age- and sex-matched controls were enrolled. Multimodal MRI, including structural, blood oxygenation level-dependent, and three-dimensional pseudo-continuous arterial spin labelling were employed. Cerebral blood flow and seed-based functional connectivity were analysed. Global and regional cerebral blood flow in several brain regions in the recurring carpal tunnel syndrome group decreased. Significant between-group differences were found in cerebral blood flow maps involving the frontal gyrus and insula, which exhibited an inverse correlation with central sensitization scores. Increased brain connectivity was noted in recurrent carpal tunnel syndrome patients and was negatively correlated with symptom severity. Individuals with chronic neuropathic pain secondary to recurrent median nerve entrapment manifested maladaptive brain networks in cortical regions involving sensory, cognitive and affective processing. Our findings may highlight new avenues for cortical biomarkers and potential mechanisms underlying central sensitization in persistent pain after peripheral neuropathy, which may facilitate innovative targeted management strategies for those who respond poorly to concurrent treatment regimes.

Keywords: carpal tunnel syndrome; functional magnetic resonance imaging; limbic system; prefrontal cortex; recurrent neuropathic pain.