Understanding the role of early life social determinants and sex-specific pubertal pathways in the development of adolescent chronic pain - PROJECT SUMMARY Chronic pain affects at least 20% of adolescents globally, significantly impairing their physical, emotional, social, and school functioning. This often leads to adversities in adulthood, including persistent pain, poor health, opioid misuse, and socioeconomic challenges. Despite its profound impact, the etiological factors in the development of adolescent chronic pain remain poorly understood. Maternal stress and family protective factors during the early life period, from conception to early childhood, are crucial in shaping long-term health outcomes and may hold key insights into the developmental roots of chronic pain. However, the lack of longitudinal studies on how multilevel maternal risk and family protective factors influence adolescent chronic pain leaves a critical gap in understanding its social determinants. Puberty is a pivotal period when chronic pain peaks, sex disparities emerge, with females disproportionately affected. Our prior research reveals that early sexual maturity heightens pain risk in both sexes, while higher testosterone levels correlate with lower pain risk in male adolescents, suggesting that divergent sex hormone exposures in males and females, along with the common experience of sexual maturation, may be key pubertal mechanisms involved in the development of adolescent chronic pain. However, how pubertal development links early life social factors to adolescent chronic pain remains unexplored. This project aims to 1) Identify longitudinal associations of early life risk and protective factors with adolescent chronic pain outcomes at ages 12 and 14, and 2) Test pubertal development mechanisms, including sex hormones and sexual maturity, as mediators of these associations. We will follow approximately 415 mother-child dyads from four sites across the United States, who are participants in the longitudinal pregnancy cohort, The Infant Development and the Environment Study (TIDES). We will evaluate the impact of maternal stress and family protective factors, measured from pregnancy through early childhood, on adolescents' sex hormones, sexual maturity, and chronic pain outcomes at ages 12 and 14. With TIDES participants currently entering puberty, our study seizes a unique and timely opportunity to pioneer the testing of life course models linking early life social determinants to adolescent chronic pain through pubertal development mechanisms. Our analytic approach follows the life course epidemiology framework, and considers three conceptual causal models - “accumulation of risk”, “chain of risk”, and “critical/sensitive period” - to determine how risk and protective factors at different stages of early life influence adolescent chronic pain. This will allow us to pinpoint key developmental social origins of chronic pain that have the potential to inform early, family-based interventions. Our focus on sex hormones and sexual maturity as key pubertal mechanisms will help identify high-risk individuals for early, targeted interventions that have the potential to improve lifelong health trajectories and reduce sex disparities in chronic pain.
