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Circulating microRNAs from the mouse tibia fracture model reflect the signature from patients with complex regional pain syndrome
Journal article   Open access   Peer reviewed

Circulating microRNAs from the mouse tibia fracture model reflect the signature from patients with complex regional pain syndrome

Jason R. Wickman, Xuan Luo, Wenwu Li, Renee Jean-Toussaint, Peyman Sahbaie, Ahmet Sacan, J. David Clark and Seena K. Ajit
Pain reports, v 6(3), pp e950-e950
01 Sep 2021
PMID: 34514274
url
https://doi.org/10.1097/pr9.0000000000000950View
Published, Version of Record (VoR)CC BY-NC-ND V4.0 Open
url
https://doi.org/10.1097/PR9.0000000000000950View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
Introduction: Complex regional pain syndrome (CRPS) often results from an initial trauma that later produces a disproportionate amount of pain. The mechanisms underlying CRPS have been studied using a tibia fracture model (TFM) in rodents because this model closely mimics symptoms and has several molecular correlates observed in patients with CRPS. Objective: Here, we determined whether the TFM has alterations in circulating microRNAs (miRNAs) and cytokines transported by small extracellular vesicles (sEVs) that faithfully model previously reported miRNA alterations from patients with CRPS. Methods: We isolated and characterized serum-derived sEVs from mice 3 weeks after fracture when symptoms such as pain hypersensitivity develop. Whole-transcriptome profiling was used to determine sEV miRNAs, and Bio-Plex Pro Mouse Cytokine 23-plex assay was used to measure cytokines. Differentially expressed miRNAs from TFM were compared with previously reported circulating miRNA alterations from patients with CRPS. Results: Although sEV cytokine levels were unchanged, there were significant changes in sEV miRNA profiles. Differentially expressed miRNAs from TFM sEVs significantly overlapped with those previously reported in patients with CRPS. Of the 57 sEV miRNAs dysregulated in the TFM, 30 were previously reported in patients with CRPS compared with healthy control donors both in sEVs and 23 in whole blood. Conclusions: These findings enhance the validity of TFM as a model for CRPS and suggest that specific miRNA dysregulation may be a shared feature of CRPS and the TFM. These dysregulated miRNAs could help identify mechanistic targets or serve as biomarker candidates for both diagnosis and treatment responses in clinical trials.

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Domestic collaboration
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Neurosciences
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