Background/Objectives: Chronic pain syndromes pose a significant global health challenge to patients and physicians with a complex relationship of biological and psychosocial factors that are only partly understood. Emerging research suggests an association between prenatal and childhood adversity and the development of somatic syndromes, particularly in females. This study aims to explore the relationship between sexual dimorphic epigenetic changes in the connectome and prenatal and early life adversity (ELA). Methods: A review of the existing literature was conducted, examining studies utilizing MRI to identify critical periods of environmental influence on neural phenotypes. Results: The findings indicate a significant association between prenatal and childhood adversity and the emergence of central sensitization syndromes, particularly among females. Notably, alterations in grey matter volume and neural connectivity patterns were observed, suggesting that early adverse experiences can influence pain signaling mechanisms. Conclusions: Understanding the role of sex differences in brain circuitry is crucial for developing personalized pain management strategies. This study highlights the importance of considering both biological and psychosocial factors in addressing chronic pain, as interventions based predominantly on male subjects may be less effective for females. Further research is warranted to explore these differences and refine therapeutic approaches.
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