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

Abstract

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.

Ion Channel Genes in Painful Neuropathies

“…Consistent with this, long noncoding kcna2 antisense RNA silenced KCNA2 and contributed to NP in rats via reducing the voltage-gated potassium current and increasing DRG excitability [61]. In addition, several studies have linked the epigenetic repression of KCNA2 with the development of NP [62][63][64][65][66][67]. Based on the above, K channels could be an appropriate target for pain therapy in specific individuals.…”

Risk factors and related miRNA phenotypes of chronic pain after thoracoscopic surgery in lung adenocarcinoma patients

“…Microarray and deep-sequencing analyses revealed that nerve injury or noxious stimuli could induce broad changes in miRNA expression in serum or along the pain processing pathways. 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 [ 15 ]. There are several studies reporting changes in miRNA expression in patients with chronic pain, such as miR-146a, let-7a, miR-145, miR-550a, miR-132 and miR-3613 [ 7 , 11 ].…”

Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms

“…These changes can lead to the abnormal discharge of neurons and subsequently result in pain. 84 Consequently, ion channels play a pivotal role in determining neuronal excitability, and they might be subject to miRNA regulation under painful conditions. It is worth noting that voltage-gated channels, implicated in the pain pathway, have become the primary focus of interventions for treating neuropathic pain.…”