Concordance of cortical morphological anomalies with genetic predisposition to multisite chronic pain in females

Korean J Pain. 2026 Apr 1;39(2):260-271. doi: 10.3344/kjp.25253.

ABSTRACT

BACKGROUND: Multisite chronic pain (MCP) is a debilitating condition disproportionately affecting females, yet its underlying biological basis, particularly the connection to brain structure and the specific role of genetic factors, remains incompletely understood.

METHODS: This study delves into the genetic correlation between MCP in females and cerebral cortical morphology, specifically concentrating on cortical thickness (CT) and surface area (SA). Leveraging genome-wide association study (GWAS) data, the investigation establishes significant genetic correlations between female MCP and diverse cerebral cortical regions.

RESULTS: The outcomes underscored that diminished CT in the frontal pole, increased CT in the rostral middle frontal cortex, and reduced SA in the superior frontal cortex exhibited nominal associations with increased susceptibility to MCP in females (P < 0.05). Conversely, MCP susceptibility demonstrated a nominal causal association with reduced CT in the parahippocampal gyrus and postcentral gyrus. Gene enrichment analysis suggests potential correlations between these genetic loci and biological pathways related to body mass index and pain phenotypes.

CONCLUSIONS: This study provided exploratory evidence of potential shared genetic pathways influencing both MCP susceptibility and cerebral cortex structure. The results suggested that alterations in brain morphology in females may have a bidirectional relationship with susceptibility to chronic pain.

PMID:41918306 | DOI:10.3344/kjp.25253