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Papers of the Week

Papers: 15 Jul 2023 - 21 Jul 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology


2023 Jul 17

J Pain


Identifying Stress-Exacerbated Thermal-Injury Induced microRNAs.


Pando M, Yang R, Dimitrov G, Chavez R, Garza T, Trevino AV, Gautam A, Stark TR, Hammamieh R, Clifford J, Sosanya NM


Using a model of Combat and Operational Stress Reaction (COSR), our lab recently showed that exposure to an unpredictable combat stress (UPCS) procedure prior to a thermal injury increases pain sensitivity in male rats. Additionally, our lab has recently shown that circulating extracellular vesicle-microRNAs (EV-miRNAs), which normally function to suppress inflammation, were down regulated in a male rat model of neuropathic pain. In this current study, male and female rats exposed to UPCS followed by thermal injury, were evaluated for changes in circulating EV-miRNAs. Adult female and male Sprague Dawley rats were exposed to an UPCS procedure for either 2 or 4 weeks. Groups consisted of the following: non-stress (NS), stress (S), NS + thermal injury (TI), and S+TI. Mechanical sensitivity was measured and plasma collected at baseline, throughout the UPCS exposure, and post thermal-injury. EV-miRNA isolation was performed, followed by small RNA sequencing and subsequent data analysis. UPCS exposure alone resulted in mechanical allodynia in both males and female rats at specific time points. Thermal-injury induction occurring at peak UPCS resulted in increased mechanical allodynia in the injured hind paw compared to thermal-injury alone. Differential expression of the EV-miRNAs was observed between the NS and S groups as well as between NS+TI and S+TI groups. Consistent differences in EV-miRNAs are detectable in both COSR as well as during the development of mechanical sensitivity and potentially serve as key regulators, biomarkers, and targets in the treatment of COSR and thermal-injury induced mechanical sensitivity. PERSPECTIVE: This article presents the effects of unpredictable combat stress and thermal injury on extracellular vesicle contained microRNAs in an animal model. These same mechanisms may exist in clinical patients and could be future prognostic and diagnostic biomarkers.