(111) - Investigating the influence of exercise and diet on early life stress-induced pain and obesity in mice

Abstract

Individuals who experience adverse childhood events show a susceptibility to developing chronic pain disorders. These disorders frequently present co-morbidly and with both mood and obesity-related metabolic disorders. Although the underlying mechanisms of these syndromes are yet to be established, it is recognized that the hypothalamic-pituitary-adrenal (HPA) axis plays a role in the regulation of the stress, nociceptive, and metabolic systems. Therefore, it is hypothesized that HPA axis dysfunction influences their pathogenesis. The present study is investigating the effect of exercise and diet interventions in a mouse model of early life stress that displays molecular evidence of altered HPA axis regulation as well as behavioral evidence of urogenital pain disorders. Neonatal maternal separation (NMS) was performed by separating entire litters from the dam for 3h/day starting on postnatal day 1 (P1) to P21. Naive pups remained undisturbed and all pups were weaned on P22. At 4 weeks of age NMS and naive mice either received free access to a running wheel in their home cage (exercised [-Ex]) or remained in sedentary housing (-Sed). Body composition analysis was assessed in adult mice using EchoMRI. Both male and female NMS-Sed mice weighed significantly more and had greater percent body fat compared to naive or Ex mice. At 16 weeks of age, male mice were placed on a high-fat/sucrose diet for one week. All groups displayed a significant increase in weight and percent body fat. Interestingly, a diet-induced increase in perigenital mechanical sensitivity was observed in all mice except for NMS-Sed, which had an increased withdrawal threshold compared to their baseline measurements. Our findings suggest that exercise can attenuate early life stress-induced development of obesity and potential metabolic syndrome. Future work will investigate the efficacy of an anti-inflammatory diet and long-term consequences of high-fat/sucrose diet consumption. Supported by NIH grants DK099611, DK103872, and HD057850.