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Adolescent multisite pain represents a significant clinical challenge that affects physical health and emotional well-being. Furthermore, recent research from the Adolescent Brain and Cognitive Development (ABCD) Study reveals that the neural mechanisms underlying this pain differ significantly between sexes. Specifically, this study examined brain structure in over 6,000 participants aged 11 to 12 years to identify these patterns.
The findings indicate that male and female youth possess distinct brain-structure associations. For instance, male adolescents showed a clear inverse linear relationship between cortical thickness and pain reporting. Specifically, lower thickness in the left pre- and postcentral gyri correlated with a higher number of reported pain sites. Consequently, these somatosensory regions appear central to the male experience of widespread pain.
Conversely, female adolescents exhibited a non-linear relationship. Researchers observed that the surface area of the right supramarginal gyrus relates to pain reporting in a more complex manner. Moreover, this highlights that the neurobiological pathways for pain in females do not follow the same structural rules as in males. Therefore, clinicians must adopt a sex-specific lens when evaluating neuroimaging data related to pain symptoms.
Pubertal status also plays a critical moderating role, particularly in males. Specifically, males in early puberty demonstrated an inverse relationship between anterior and mid cingulate cortex thickness and pain sites. However, this relationship became positive for those who had progressed beyond mid-puberty. Additionally, this shift suggests that hormonal and developmental changes significantly reshape the brain's pain-processing networks during the transition into late adolescence.
Male adolescents often show an inverse relationship between cortical thickness in sensorimotor areas and pain sites. In contrast, females exhibit non-linear patterns involving the surface area of the supramarginal gyrus.
Yes, particularly in males. The relationship between cingulate cortex thickness and pain reporting can flip from negative to positive as an individual moves through different stages of puberty.
Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice or a professional relationship. Always seek the advice of a qualified healthcare provider for any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Hidalgo-Lopez E et al. Cortical thickness, surface area, and multisite pain: distinct patterns by sex in adolescence. Biol Sex Differ. 2026 Apr 06. doi: 10.1186/s13293-026-00898-6. PMID: 41943162.
Risley S, et al. Neurobiological antecedents of multisite pain in children. PAIN. 2022;163(4):711-722. doi: 10.1097/j.pain.0000000000002431.
Casey BJ, et al. The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites. Dev Cogn Neurosci. 2018;32:43-54.

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