Journal article
Analgesic Response to Intravenous Ketamine Is Linked to a Circulating microRNA Signature in Female Patients With Complex Regional Pain Syndrome
The journal of pain, v 16(9), pp 814-824
Sep 2015
PMID: 26072390
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although ketamine is beneficial in treating complex regional pain syndrome (CRPS), a subset of patients respond poorly to therapy. We investigated treatment-induced microRNA (miRNA) changes and their predictive validity in determining treatment outcome by assessing miRNA changes in whole blood from patients with CRPS. Blood samples from female patients were collected before and after 5 days of intravenous ketamine administration. Seven patients were responders and 6 were poor responders. Differential miRNA expression was observed in whole blood before and after treatment. In addition, 33 miRNAs differed between responders and poor responders before therapy, suggesting the predictive utility of miRNAs as biomarkers. Investigation of the mechanistic significance of hsa-miR-548d-5p downregulation in poor responders showed that this miRNA can downregulate UDP-glucuronosyltransferase UGT1A1 mRNA. Poor responders had a higher conjugated/unconjugated bilirubin ratio, indicating increased UGT1A1 activity. We propose that lower pretreatment levels of miR-548d-5p may result in higher UDP-GT activity, leading to higher levels of inactive glucuronide conjugates, thereby minimizing the therapeutic efficacy of ketamine in poor responders. Differences in miRNA signatures can provide molecular insights distinguishing responders from poor responders. Extending this approach to other treatment and outcome assessments might permit stratification of patients for maximal therapeutic outcome.
This study suggests the usefulness of circulating miRNAs as potential biomarkers. Assessing miRNA signatures before and after treatment demonstrated miRNA alterations from therapy; differences in miRNA signature in responders and poor responders before therapy indicate prognostic value. Mechanistic studies on altered miRNAs can provide new insights into disease.
•We studied ketamine treatment–induced miRNA alterations in blood from patients with CRPS.•Differential miRNA expression was observed in whole blood before and after treatment.•Before therapy, 33 miRNAs differed between responders and poor responders.•Lower pretreatment levels of miR-548d-5p may contribute to higher UDP-GT activity.•Circulating miRNAs can be potential biomarkers in predicting treatment response.
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Details
- Title
- Analgesic Response to Intravenous Ketamine Is Linked to a Circulating microRNA Signature in Female Patients With Complex Regional Pain Syndrome
- Creators
- Sabrina R Douglas - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaBotros B Shenoda - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaRehman A Qureshi - School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PennsylvaniaAhmet Sacan - School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PennsylvaniaGuillermo M Alexander - Department of Neurology, Drexel University College of Medicine, Philadelphia, PennsylvaniaMarielle Perreault - Department of Neurology, Drexel University College of Medicine, Philadelphia, PennsylvaniaJames E Barrett - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PennsylvaniaEnrique Aradillas-Lopez - Department of Neurology, Drexel University College of Medicine, Philadelphia, PennsylvaniaRobert J Schwartzman - Department of Neurology, Drexel University College of Medicine, Philadelphia, PennsylvaniaSeena K Ajit - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- The journal of pain, v 16(9), pp 814-824
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]; Neurology
- Web of Science ID
- WOS:000361166200002
- Scopus ID
- 2-s2.0-84940788904
- Other Identifier
- 991014878425204721
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- Web of Science research areas
- Clinical Neurology
- Neurosciences