The etiological roles of miRNAs, lncRNAs, and circRNAs in neuropathic pain: A narrative review

BACKGROUND: Non‐coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain‐related ncRNAs expression changes, including microRNAs (miRNAs), long non‐coding RNAs (lncRNAs), and circular non‐coding RNAs (circRNAs). METHODS: We searched two databases, PubMed and GeenMedical, for relevant studies. RESULTS: Peripheral nerve injury or noxious stimuli can induce extensive changes in the expression of ncRNAs. For example, higher serum miR‐132‐3p, ‐146b‐5p, and ‐384 was observed in neuropathic pain patients. Either sciatic nerve ligation, dorsal root ganglion (DRG) transaction, or ventral root transection (VRT) could upregulate miR‐21 and miR‐31 while downregulating miR‐668 and miR‐672 in the injured DRG. lncRNAs, such as early growth response 2‐antisense‐RNA (Egr2‐AS‐RNA) and Kcna2‐AS‐RNA, were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively. Dysregulated circRNA homeodomain‐interacting protein kinase 3 (circHIPK3) in serum and the DRG, abnormally expressed lncRNAs X‐inactive specific transcript (XIST), nuclear enriched abundant transcript 1 (NEAT1), small nucleolar RNA host gene 1 (SNHG1), as well as ciRS‐7, zinc finger protein 609 (cirZNF609), circ_0005075, and circAnks1a in the spinal cord were suggested to participate in neuropathic pain development. Dysregulated miRNAs contribute to neuropathic pain via neuroinflammation, autophagy, abnormal ion channel expression, regulating pain‐related mediators, protein kinases, structural proteins, neurotransmission excitatory–inhibitory imbalances, or exosome miRNA‐mediated neuron–glia communication. In addition, lncRNAs and circRNAs are essential in neuropathic pain by acting as antisense RNA and miRNA sponges, epigenetically regulating pain‐related molecules expression, or modulating miRNA processing. CONCLUSIONS: Numerous dysregulated ncRNAs have been suggested to participate in neuropathic pain development. However, there is much work to be done before ncRNA‐based analgesics can be clinically used for various reasons such as conservation among species, proper delivery, stability, and off‐target effects.