Comorbid Chronic Pain, Mood, and Metabolic Disorders Arising from Early Life Stress Exposure in Mice

Exposure to early life stress has a significant and long-lasting impact on health outcomes later in life, leading to increased morbidity and mortality. Adults who report high adverse childhood events scores are more likely to present with chronic pain, mood disorders, obesity, and/or metabolic syndrome. Outcomes due to early life stress are largely attributed to alterations within the hypothalamic-pituitary-adrenal (HPA) axis, which lead to changes in glucocorticoid production, responsivity, and signaling. The hippocampus is an important negative regulator of HPA axis function and is especially susceptible to early life stress exposure. Our laboratory has developed and characterized a mouse model of neonatal maternal separation (NMS) to study outcomes related to early life stress. Here, we will present data demonstrating that NMS mice display evidence of urogenital hypersensitivity, as well as migraine-like behaviors, altered anxiety- and depressive-like behaviors, and increased adiposity both on a chow and high fat/high sucrose diet. Results from magnetic resonance imaging/spectroscopy (MRI/MRS) studies, as well as immunohistochemical investigation, have revealed decreased gray matter volume and neurogenesis in the hippocampus of NMS mice. Together, these results suggest that NMS in mice may provide an important translational model for understanding the mechanisms that contribute to early life stress-induced outcomes.