Chronic pain (i.e., pain lasting > 3 months) is an intergenerational problem; it is transmitted across generations and is influenced adversity and trauma experienced early in life. Pain and mental health are closely linked. Youth with chronic pain and their parents experience trauma, adversity, and mental health issues at higher rates than non-pain populations. Biopsychosocial and mutual-maintenance conceptual models of chronic pain posit that neurobiological, cognitive-behavioral, and social factors drive the chronic pain-mental health relationship across generations; however, this has not yet been empirically shown in prospective research longitudinal research spanning childhood and adolescence. We have new emerging birth cohort data that provides compelling evidence that early adverse childhood experiences of parents influence the development and maintenance of chronic pain in adolescents, and are identifying key mechanisms underlying this transmission. Dr. Noel will present new data from a large birth cohort [n=3000] showing that adverse childhood experiences of parents influence the development and maintenance of chronic pain in youth and these relationships are either buffered or exacerbated by psychological and social factors. Findings will be tied to findings from two studies using preclinical rodent models demonstrating how early life stress before (in mothers during pregnancy) and at birth (in pups) leads to pain problems in adolescence through key epigenetic, inflammatory, neurobiological and microbiome changes. Implications for tailored, integrated interventions and prevention approaches targeting psychological and social factors to break the intergenerational cycle of pain will be discussed.