Location: Microbiome and Metabolism Research
Title: High-resolution metabolic profiling of the effects of early-life stress after peripheral nerve injuryAuthor
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RODRIGUEZ, KAYLEIGH - University Arkansas For Medical Sciences (UAMS) |
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BISHOP, MARY GRACE - University Arkansas For Medical Sciences (UAMS) |
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OSBORN, LAURA - University Arkansas For Medical Sciences (UAMS) |
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REDLING, DAKOTA - University Arkansas For Medical Sciences (UAMS) |
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SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC) |
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PORTER, CRAIG - Arkansas Children'S Nutrition Research Center (ACNC) |
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Yeruva, Venkat |
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STEPHENS, KIMBERLY - University Arkansas For Medical Sciences (UAMS) |
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Submitted to: The Journal of Pain
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/19/2026 Publication Date: 3/31/2026 Citation: Rodriguez, K.A., Bishop, M., Osborn, L.R., Redling, D., Sikes, J.D., Porter, C., Yeruva, V., Stephens, K.E. 2026. High-resolution metabolic profiling of the effects of early-life stress after peripheral nerve injury. The Journal of Pain. 44 (2026): Article 106270. https://doi.org/10.1016/j.jpain.2026.106270. DOI: https://doi.org/10.1016/j.jpain.2026.106270 Interpretive Summary: Mounting evidence supports an association between chronic pain and the promotion of metabolic disorders including weight gain and loss of fat free mass. Indeed, altered levels of carbohydrate, lipid, protein and nucleic acid metabolites, which are involved in key cellular process and the trajectory of individual health, are well documented in individuals living with chronic pain. However, it is unknown whether the long-term impact of pain-promoting metabolic changes are further exacerbated by the presence of environmental factors such as stress in early life. Our study demonstrated that early life stress (ELS) in the setting of nerve-injury induced pain influences pain sensitivity, behavioral response and metabolic outcomes. Technical Abstract: 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 (ELS) is an environmental risk factor that is well known to influence pain susceptibility. However, the maladaptive effects of ELS on metabolism in the setting of chronic pain is unknown. In this study, we used the well-established limited bedding model of ELS and subjected male and female adult offspring and controls to high-resolution 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 ELS. 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 ELS increases mechanical hypersensitivity following peripheral nerve injury and identify sexual dimorphic relationships between ELS and pain behaviors where ELS reduces energy expenditures after peripheral nerve injury only in males. 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. |
