MicroRNA Expression Analysis of the Rat Brain During Neuropathic Pain Development

Abstract

Background Approximately 40% of Service Members deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) and an astounding 80% of Veterans overall report experiencing pain. Currently, drugs that adequately treat pain may result in addiction and substance abuse or negative side effects such as nausea, vomiting, renal and cardiovascular issues, among other physiological and cognitive problems. Inadequate acute pain management can lead to the development of chronic pain. Combat and non-combat injuries, acute and chronic pain all have the potential to impact return-to-duty rates/decisions, thereby negatively affecting the Fighting Force. To develop more effective pain therapeutics, the molecular mechanisms contributing to the development of neuropathic pain are under intense investigation and further research is needed to fully understand neuropathic pain induction and maintenance. The overarching objective of this study is to identify microRNA (miRNA) changes in key brain regions during the onset and progression of neuropathic pain in a rodent model. Results Changes in miRNA expression were observed at day 15 post-SNL in the amygdala and thalamus. The majority of changes were observed in the left side of the brain, contralateral to the right-sided SNL injury. The DE miRNAs identified mainly in the amygdala and thalamus did not overlap between brain regions. The altered miRNAs regulate key signaling pathways and genes important in pain development. Discussion The majority of epigenetic studies investigating altered miRNA expression in the pain field have explored the peripheral nervous system. Very few studies have evaluated miRNA dynamics in the brain following neuropathic pain development. This study provides key insights into changes occurring in the brain following peripheral nerve injury. Our lab has previously identified circulating extracellular vesicle (EV) miRNAs that are altered in the blood post-SNL. There is some overlap between the blood and brain miRNAs that may serve as key biomarkers in prognosis and/or diagnosis of a peripheral nerve injury and the development of chronic pain.