RP11-819C21.1 and ZNRD1-AS long non-coding RNA changes following painful laser stimulation correlate with pain habituation in healthy subjects: A laser evoked potential (LEP) study

Abstract

Long non-coding RNAs (lncRNAs) are a group of 200 nucleotides acting as regulators of gene expression implicated in various diseases such as cancer, cardiovascular diseases, autoimmune and neurodegenerative disorders. Moreover, lncRNAs are involved in pain modulation. We recorded LEPs in order to study: (1) lncRNAs modifications in experimental pain model; (2) correlation between the lncRNA changes and objective measure of pain perception. LEPs were recorded in 12 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 obtained immediately before LEP recording (baseline) and after 30-min (post-pain). We screened 84 lncRNAs, involved in autoimmunity and inflammatory response. Two lncRNAs were up-regulated after pain: RP11-819C21.1 (fold change = 8.2; p = 0.038) and ZNRD1 antisense-RNA1 non-protein coding (ZNRD1-AS) (fold change = 6.3; p = 0.037). lncRNAs up-regulated showed a significant positive correlation with perioral LEP habituation (p = 0.04 and p = 0.01, respectively). 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 andmiR19b, 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.