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.
Circulating microRNAs from the mouse tibia fracture model reflect the signature from patients with complex regional pain syndrome
Creators
Jason R. Wickman - Drexel University
Xuan Luo - Drexel University
Wenwu Li - Vet Affairs Palo Alto Hlth Care Syst, Anesthesiol Serv, Palo Alto, CA USA
Renee Jean-Toussaint - Drexel University
Peyman Sahbaie - VA Palo Alto Health Care System
Ahmet Sacan - Drexel University
J. David Clark - VA Palo Alto Health Care System
Seena K. Ajit - Drexel University
Publication Details
Pain reports, v 6(3), pp e950-e950
Publisher
Lippincott Williams & Wilkins
Number of pages
12
Grant note
R01NS102836; R01NS117340 / NIH NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
I01RX001475 / Department of Veterans Affairs; US Department of Veterans Affairs
Resource Type
Journal article
Language
English
Academic Unit
Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
Web of Science ID
WOS:000711754400010
Scopus ID
2-s2.0-85137411039
Other Identifier
991019168400404721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool: