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Contains fulltext : 230742.pdf (Publisher’s version ) (Open Access) Although adverse early experiences prime individuals to be at increased risk for chronic pain, little research has examined the trauma-pain relationship in early life or the underlying mechanisms that drive pathology over time. Given that early experiences can potentiate the nociceptive response, this study aimed to examine the effects of a high-fat high-sugar (HFHS) diet and early life stress (maternal separation; [MS]) on pain outcomes in male and female adolescent rats. Half of the rats also underwent a plantar-incision surgery to investigate how the pain system responded to a mildly painful stimuli in adolescence. Compared to controls, animals on the HFHS diet, experienced MS, or had exposure to both, exhibited increased anxiety-like behavior and altered thermal and mechanical nociception at baseline and following the surgery. Advanced MRI demonstrated that the HFHS diet and MS altered maturation of the brain, leading to changes in brain volume and diffusivity within the anterior cingulate, amygdala, corpus callosum, nucleus accumbens, and thalamus, while also modifying integrity of the corticospinal tracts. The effects of MS and HFHS diet were often cumulative, producing exacerbated pain sensitivity and increased neurobiological change. As early experiences are modifiable, understanding their role in pain may provide targets for early intervention/prevention. 15 p.