The influence of diet and exercise on early life stress-induced co-morbid disorders in mice

Individuals with functional pain disorders often present with symptoms of or are diagnosed with more than one disorder. Furthermore, these patients with co-morbid pain disorders are also more likely to present with mood disorders, including depression and anxiety, as well as with obesity-related metabolic syndrome. Exposure to stress or adversity early in life increases the risk of developing co-morbid chronic pain, mood, and obesity-related metabolic syndrome in adulthood. This may be due to altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response, alters our perception of pain, and has downstream metabolic effects. The overall goals of this dissertation are to expand our studies on the many consequences of early life stress and investigate potential non-pharmacological treatment options for patients with these disorders including exercise and an anti-inflammatory diet (AID). To do this, I use a mouse model of early life stress, neonatal maternal separation (NMS), which exhibits increased urogenital sensitivity as well as altered limbic regulation of the HPA axis. This dissertation investigates the susceptibility of female NMS and non-stressed (naïve) sedentary (Sed) and exercised (Ex) mice to evoked migraine like-behaviors and the susceptibility of male NMS- and naïve-Sed and –Ex mice to the development of high-fat/high-sucrose diet-induced obesity-related metabolic syndrome. I focus on migraine and obesity-related metabolic syndrome due to the high clinical incidence of these disorders in chronic urogenital pain patients. Finally, I evaluate the effect of AID on putative early life stress0induced co-morbid disorders in female and male mice. This work provides insight into the significant influence that environmental factors such as early life stress, diet, and exercise have on the development of chronic disorders as well as the complex interactions of these factors. Additionally, this research reveals sex differences in stress, pain, and metabolic pathways. These studies are novel because each combines multiple environmental factors in an attempt to mimic human lifestyle choices to study chronic pain disorders, obesity-related metabolic syndrome, and co-morbidity