Cortical thickness, surface area, and multisite pain: distinct patterns by sex in adolescence

Biol Sex Differ. 2026 Apr 6. doi: 10.1186/s13293-026-00898-6. Online ahead of print.

ABSTRACT

BACKGROUND: Multisite pain is common during adolescence and is influenced by sex-related neurobiological and developmental factors, but its developmental neural mechanisms are unclear.

METHODS: Utilizing data from the Adolescent Brain and Cognitive Development Study, we investigated the relation between cortical brain structure and multisite pain (assessed by youth self-reports of painful regions on a body map) in male (N = 3,299) and female (N = 2,844) adolescents aged 11-12 years. We focused on brain regions functionally linked to multisite pain (i.e., bilateral sensorimotor, cingulate, fronto-insular and inferior parietal cortex). We also explored the moderating role of pubertal status (assessed by the Pubertal Development Scale).

RESULTS: Findings revealed distinct brain structure-pain associations in male and female youth. Male youth exhibited an inverse linear relation between cortical thickness of the left pre- and postcentral gyri and number of pain sites. Female youth exhibited a non-linear relation between surface area of the right supramarginal gyrus and number of pain sites. Pubertal status moderated the cingulate cortical thickness-pain association in males; those in early puberty had an inverse relation between anterior and mid cingulate cortex thickness and pain sites, whereas this relation was positive in those beyond mid-puberty.

CONCLUSION: This study provides valuable insights into the sex-dependent neural organization linked to adolescent pain.

PMID:41943162 | DOI:10.1186/s13293-026-00898-6