P46-S RP11-819C21.1 and ZNRD1-AS long non-coding RNA changes following experimental pain correlate with laser-evoked potential habituation

Abstract

Background Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs acting as regulators of gene expression, through interaction with histones or through interaction with complementary DNA sequences, implicated in various human diseases such as cancer, cardiovascular diseases, autoimmune and neurodegenerative disorders and have been reported to be involved in the modulation of neuropathic pain. We recorded Laser Evoked Potentials (LEPs) in order to study: (1) lncRNAs modifications in experimental pain model; (2) correlation between the lncRNA changes and objective measure of pain perception. Material and methods LEPs were recorded in 11 healthy subjects after hand and perioral region stimulation. Three consecutive series were recorded for each stimulation site in order to investigate the habituation. Blood samples were collected immediately before LEP recording (baseline) and after 30-min (post-pain). We screened 84 lncRNAs, involved in autoimmunity and inflammatory response. Results We identified 2 lncRNAs up-regulated at the post-pain time: RP11-819C21.1 (fold change = 8.2; p = 0.038) and ZNRD1 antisense RNA 1 non-protein coding (ZNRD1-AS) (fold change = 6.3; p = 0.037). The up-regulation of both lncRNAs showed a significant positive correlation with the LEP habituation to perioral region stimulation (p = 0.04 and p = 0.01, respectively). Conclusions This is the first study showing lncRNA changes in a pain experimental model. RP11-819C21.1 and ZNRD1-AS shows as direct target miR-19a and miR19b, a class of microRNAs involved in modulation of multiple potassium channel α-subunits. lncRNAs could be involved in the pathophysiology of painful diseases characterized by reduced habituation to pain.