Pain is one of the most common reasons to seek medical attention and chronic pain is a worldwide epidemic. Under some circumstances, incoming protective nociceptive signaling is prolonged leading to clinical manifestations of pathological neuronal signaling. The chronic constriction injury (CCI) of the sciatic nerve is a widely used preclinical model of pathological neuropathic pain. Over the past decade, investigators have come to appreciate the extracellular actions of RNA located within cells such as mRNA, micro (mi) RNA, and other long and short noncoding (nc) RNAs. The development and/or maintenance of chronic pain could be controlled epigenetically through ncRNAs. Here we seek to characterize ncRNAs in blood, sciatic nerve, and spinal cord in a mouse model of neuropathic pain as this may serve to elucidate potential biomarkers relevant to pathological pain in humans. Male C57BL6/J mice (6 CCI and 6 sham procedure) underwent surgery for sciatic nerve ligation with chromic gut sutures. Following 7 days, mechanical allodynia was quantified using the von Frey assay. Mice were then euthanized for collection of spinal cord, sciatic nerve, and blood. cDNA was synthesized to 322 unique mature miRNAs from the total RNA. Of the 627 miRNAs examined, 414 and 376 were detectable (CT ≤ 35) in the spinal column and sciatic nerve, respectively. In the CCI mice that displayed mechanical allodynia, 11 and 126 miRNAs were differentially expressed (i.e., greater than 1.5‐fold increase or decrease; P < 0.05) in the spinal column and sciatic nerve, respectively, as compared to sham controls. Three members of the miR‐183 cluster (miR‐183, miR‐182 and miR‐96) were reduced in both the spinal column and sciatic nerve. Our data support the use of miRNAs as biomarkers to identify subpopulations of patients with neuropathic pain. Further, targeting miRNAs may hold promise for the treatment of pathological pain.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.