Potential application of long non–coding RNAs for pain therapy as therapeutic targets and biomarkers

Long non–coding RNAs (lncRNAs), which are generally defined as non–coding RNAs that are longer than 200 nucleotides, have recently emerged as an important regulator of pain. Most lncRNAs exhibit tissue– or even cell type–specific expression, and a large number of lncRNAs are preferentially expressed in the nervous system, suggesting their importance in neurological functions. Accordingly, expression changes of lncRNAs in the somatosensory nervous system have been reported in various pain disorders. lncRNAs affect various gene expression processes, including epigenetic regulation and transcription, through interaction with DNA, RNA and protein at several subcellular compartments. Dysregulation of lncRNAs significantly impacts pain perception by affecting mechanisms relevant to pain, including neuronal excitability and neuroinflammation. Intriguingly, lncRNAs are released into the extracellular space with encapsulated in extracellular vesicles, such as exosome. The extracellular lncRNAs may have a role in regulating nociceptive signaling through intercellular communication, as with other non–coding RNAs such as microRNAs. In addition, extracellular lncRNAs that entered the bloodstream have great potential as diagnostic biomarkers for pain disorders. In this review, we summarize current insights into potential applications of lncRNAs as an analgesic target and a biomarker in pain disorders.