The Endometriosis–Brain Connection

Endometriosis-associated pain is linked to age-related differences in brain structure

Key Points

Highlights:

• Endometriosis-associated pain is linked to differences in brain structure, particularly in regions involved in pain processing and sensorimotor integration.
• Brain structural patterns vary by age, with distinct associations observed in adolescents and adults.

Importance:

• Demonstrating age-dependent brain structural differences in individuals with endometriosis highlights the need to consider neurodevelopmental and central pain mechanisms when evaluating and managing the disease.

What's Done Here?

• A cross-sectional neuroimaging study was conducted in individuals with surgically confirmed endometriosis, including both adolescents and adults.
• Structural brain MRI was used to assess cortical thickness, surface area, and subcortical volumes.
• Brain measures were analyzed in relation to age and pain status, with appropriate statistical adjustment.

Key Results:

• Individuals with endometriosis showed altered cortical and subcortical brain structures compared with controls.
• Several brain regions demonstrated significant age–group interactions, indicating different neurostructural patterns across developmental stages.
• Associations were observed in regions implicated in pain perception, motor control, and sensory processing.
• Findings were independent of peripheral disease characteristics, suggesting a central component to pain experience.

 Strengths and Limitations:

• Strengths include the use of surgically confirmed endometriosis, reducing diagnostic misclassification, and a developmental approach that examines adolescents and adults separately. The study applies high-resolution structural MRI with detailed regional analyses, allowing identification of age-dependent brain–pain associations beyond pelvic disease features.
• Limitations are the cross-sectional design, which precludes causal inference, and the inability to determine whether brain structural differences precede or result from chronic pain. Clinical heterogeneity, including pain duration and treatment exposure, could not be fully controlled, and neuroimaging findings cannot be directly translated into individual clinical decision-making. 

From the Editor-in-Chief – EndoNews

"This study represents an important step forward in reframing endometriosis-associated pain as a condition that cannot be fully understood through pelvic pathology alone. By focusing on structural brain measures and explicitly modeling age-related effects, the authors address a critical and often neglected dimension of endometriosis: how pain interacts with neurodevelopment and brain maturation.

The central strength of this work lies in its methodological rigor and restraint. The inclusion of surgically confirmed endometriosis, the separation of adolescents and adults, and the use of high-resolution structural MRI allow the authors to interrogate brain–pain associations without conflating diagnostic uncertainty or developmental stage. The observed age-dependent differences in cortical and subcortical regions involved in pain processing, sensorimotor integration, and cognitive control underscore that endometriosis-associated pain is not a static phenomenon, but one that may evolve across the lifespan.

Equally important is what the study does not claim. The authors avoid causal inference and do not frame endometriosis pain as a brain-originating disorder. Instead, their findings are consistent with the concept of central nervous system adaptation to persistent pain, a model well established in other chronic pain conditions. The lack of association between brain structure and peripheral disease characteristics further challenges the assumption that lesion burden alone explains pain severity.

Clinically, these data reinforce the need for age-aware and mechanism-informed pain assessment in endometriosis, particularly in adolescents, where early pain exposure may intersect with ongoing brain development. From a research perspective, the study highlights the urgency of longitudinal designs capable of disentangling predisposition from pain-related neuroplasticity.

In sum, this work advances the field by moving beyond descriptive neuroimaging toward a developmentally informed understanding of pain in endometriosis. It calls for a shift from anatomy-centered thinking to integrated models that recognize pain as a dynamic interaction between peripheral disease and the central nervous system—without oversimplification and without overstatement."

Lay Summary

A study published in Communications Biology (Nature Portfolio), the teaam led by Dr. Scott Holmes at Boston Children’s Hospital and Harvard Medical School, explored whether long-standing endometriosis-associated pain is linked to differences in brain structure, and whether these patterns vary with age.

The researchers studied adolescents and adults with surgically confirmed endometriosis and compared them with individuals who had no endometriosis and no pelvic pain. Using advanced brain MRI, they examined brain regions involved in pain processing, movement, and sensory integration, and analyzed how these regions change across adolescence and adulthood.

They found that people with endometriosis-associated pain showed distinct, age-related differences in brain structure, particularly in areas linked to pain regulation and cognitive control. Some brain regions showed patterns that changed with age only in participants with endometriosis, suggesting that the timing and duration of pain exposure may influence how the brain adapts over time.

Although endometriosis is not a brain disease or that brain changes cause the condition, findings indicate that persistent pain may be accompanied by adaptive changes in the central nervous system, which could help explain why pain severity does not always match the extent of pelvic disease.

Overall, this study supports a more integrated view of endometriosis-associated pain—one that recognizes both pelvic pathology and central pain mechanisms, particularly during sensitive developmental periods such as adolescence.

.

Research Source: https://pubmed.ncbi.nlm.nih.gov/41266551/