Increased H19 Long Non-coding RNA Expression in Schwann Cells in Peripheral Neuropathic Pain

Abstract

Background: Neuropathic pain is an intractable chronic pain condition caused by damage to the somatosensory system. Although non-coding RNAs such as microRNAs are important regulators of neuropathic pain, the role of long non-coding RNAs (lncRNAs) is poorly understood. Methods: This study used a rat model of neuropathic pain induced by lumbar fifth spinal nerve ligation (SNL). Microarray analysis of lncRNAs in the lumbar fifth dorsal root ganglion was performed at day 14 after SNL. Expression levels of H19 were examined by using quantitative PCR. In situ hybridization was used to determine the distribution of H19 at day 14 after SNL. Schwann cells were isolated from peripheral nerves at day 14 after SNL. Results: H19 lncRNA was greatly increased in the L5 dorsal root ganglion at day 14 after SNL and was significantly higher at and after day 4. In the dorsal root ganglion, H19 was detected mainly in nonneuronal cells but not in primary sensory neurons. Consistent with this, H19 expression was upregulated in Schwann cells isolated from peripheral nerves after SNL. Conclusion: Increased H19 lncRNA in Schwann cells might be involved in neuropathic pain.

<p>Long Noncoding RNA H19 Induces Neuropathic Pain by Upregulating Cyclin-Dependent Kinase 5-Mediated Phosphorylation of cAMP Response Element Binding Protein</p>

“…27 In a previous study, it was discovered that in NP patients, H19 was consistently increased in Schwann cells from the peripheral axon in the primary sensory neurons, suggesting that H19 played a pivotal role in NP pathogenesis. 10 In this study, we hypothesized that there is a mechanism of H19 in NP regulating CDK5 and CREB phosphorylation. Consequently, our data showed that silencing H19 mitigated NP by downregulating CDK5-mediated CREB phosphorylation.…”

“…9 H19 expression is increased in Schwann cells of the NP model after spinal nerve ligation. 10 Typically, CDKs that are activated together with a regulatory subunit tend to be proline-guided serine protein kinases. 11 However, CDK5 mainly functions in the central nervous system instead of the cell cycle.…”

Non-coding RNAs in neuropathic pain

“…is time-dependent and varies between strains and species [182,183,185]. LncRNAs play important roles in neuropathic pain processes not only in neurons, but also in non-neuronal cells, such as Schwann cells, satellite glial cells, macrophages and microglia [74,83,185,[188][189][190][191].…”

Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain

“…They relieved hyperalgesia and decreased neuroinflammation by modulating the P2X 3 receptor or P2X 7 receptor. In addition to the lncRNAs reported above, some lncRNAs have also been reported to be associated with NP [19,[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138].…”