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Circulating microRNA Signatures in Rodent Models of Pain

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Abstract

MicroRNAs (miRNAs) remain stable in circulation and have been identified as potential biomarkers for a variety of conditions. We report miRNA changes in blood from multiple rodent models of pain, including spinal nerve ligation and spared nerve injury models of neuropathic pain; a complete Freund’s adjuvant (CFA) model of inflammatory pain; and a chemotherapy-induced model of pain using the histone deacetylase inhibitor JNJ-26481585. The effect of celecoxib, a cyclooxygenase-2-selective nonsteroidal anti-inflammatory drug, was investigated in the CFA model as proof of principle for assessing the utility of circulating miRNAs as biomarkers in determining treatment response. Each study resulted in a unique miRNA expression profile. Despite differences in miRNAs identified from various models, computational target prediction and functional enrichment have identified biological pathways common among different models. The Wnt signaling pathway was affected in all models, suggesting a crucial role for this pathway in the pathogenesis of pain. Our studies demonstrate the utility of circulating miRNAs as pain biomarkers and suggest the potential for rigorous forward and reverse translational approaches. Evaluating alterations in miRNA fingerprints under different pain conditions and after administering therapeutic agents may be beneficial in evaluating clinical trial outcomes, predicting treatment response, and developing correlational outcomes between preclinical and human studies.

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Acknowledgments

We thank Dr. Huijuan Hu for critical reading of the manuscript.

Funding

This work was supported by a grant from the Rita Allen Foundation to Seena Ajit.

Compliance with Ethical Standards

The study was approved by the Institutional Animal Care and Use Committee of Drexel University College of Medicine and the experiments were performed in accordance with the guidelines of the National Institutes of Health.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Biomedical Engineering, Drexel University, Philadelphia, PA, 19104, USA

    Rehman A. Qureshi & Ahmet Sacan

  2. Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA, 19104, USA

    Rehman A. Qureshi

  3. Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA

    Yuzhen Tian, Marguerite K. McDonald, Kathryn E. Capasso, Sabrina R. Douglas, Ruby Gao, Irina A. Orlova, James E. Barrett & Seena K. Ajit

  4. Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Marguerite K. McDonald

  5. Albany Medical College, Albany, NY, 12208, USA

    Kathryn E. Capasso

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  1. Rehman A. Qureshi
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Correspondence to Seena K. Ajit or Ahmet Sacan.

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Qureshi, R.A., Tian, Y., McDonald, M.K. et al. Circulating microRNA Signatures in Rodent Models of Pain. Mol Neurobiol 53, 3416–3427 (2016). https://doi.org/10.1007/s12035-015-9281-4

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