title: Circulating microRNA Signatures in Rodent Models of Pain.
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.
authors.affiliation: School of Biomedical Engineering, Drexel University, Philadelphia, PA, 19104, USA.|Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA, 19104, USA.
authors.forename: Rehman A
authors.initials: RA
authors.lastname: Qureshi
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.|Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Marguerite K
authors.initials: MK
authors.lastname: McDonald
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.|Albany Medical College, Albany, NY, 12208, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Capasso
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
authors.forename: Sabrina R
authors.initials: SR
authors.lastname: Douglas
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
authors.forename: Ruby
authors.initials: R
authors.lastname: Gao
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Orlova
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Barrett
authors.affiliation: Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA. seena.ajit@drexelmed.edu.
authors.forename: Seena K
authors.initials: SK
authors.lastname: Ajit
authors.affiliation: School of Biomedical Engineering, Drexel University, Philadelphia, PA, 19104, USA. ahmet.sacan@drexel.edu.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Sacan
mesh_terms: D000818:Animals; D000068579:Celecoxib / Q000494:pharmacology; D000074166:Circulating MicroRNA / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D006930:Hyperalgesia / Q000097:blood / Q000150:complications / Q000235:genetics; D007249:Inflammation / Q000473:pathology; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000601:surgery; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013127:Spinal Nerves / Q000187:drug effects / Q000601:surgery; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D000074166:Circulating MicroRNA; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C541788:quisinostat; D005620:Freund's Adjuvant; D000068579:Celecoxib
keywords: Animal models; Biomarker; Micro-RNA; Pain