High-resolution metabolic profiling of the effects of early-life stress after peripheral nerve injury

Current evidence supports an association between chronic pain and the promotion of metabolic disorders, which can be further exacerbated by environmental factors. Early-life stress is an environmental risk factor that is well known to influence pain susceptibility. However, the maladaptive effects of early life stress on metabolism in the setting of chronic pain is unknown. In this study, we used the well-established limited bedding model of early life stress and subjected male and female adult offspring and controls to metabolic and behavioral profiling before and after peripheral nerve injury. We provide continuous, two-week, high-resolution profiling of animal food and water intake, physical movement, and energy expenditure data to study the effects of nerve injury-induced pain on metabolic outcomes in adult rats following exposure to early life stress. Additionally, we differentiate between dark and light cycles, which is crucial for understanding circadian rhythms in rodents. All offspring are assessed for baseline and post-injury mechanical sensitivity. We find that early life stress increases mechanical hypersensitivity following peripheral nerve injury in female offspring and reduces energy expenditures after peripheral nerve injury in male offspring. Our data provide valuable insights into metabolic and behavioral responses following nerve injury and contribute to understanding chronic pain development in both male and female rats. However, future studies are needed to understand the impact of our findings toward the promotion of metabolic disorders observed clinically. PERSPECTIVE: Mounting evidence supports associations between chronic pain and the promotion of metabolic disorders. We provide comprehensive metabolic assessments of the impact of ELS in the setting of nerve-injury induced pain to deepen our understanding of the mechanisms by which ELS influences pain sensitivity and metabolic outcomes after nerve injury.