Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Department of Anesthesiology, The Central Hospital Of Enshi Tujia And Miao Autonomous Prefecture, Enshi Clinical College Of Wuhan University, Enshi, Hubei, China.
J Cell Physiol. 2019 Dec;234(12):22234-22241. doi: 10.1002/jcp.28790. Epub 2019 May 26.
Neuropathic pain has been reported as a type of chronic pain due to the primary dysfunction of the somatosensory nervous system. It is the most serious types of chronic pain, which can lead to a significant public health burden. But, the understanding of the cellular and molecular pathogenesis of neuropathic pain is barely complete. Long noncoding RNAs (lncRNAs) have recently been regarded as modulators of neuronal functions. Growing studies have indicated lncRNAs can exert crucial roles in the development of neuropathic pain. Therefore, our present study focused on the potential role of the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) in neuropathic pain progression. Firstly, a chronic constrictive injury (CCI) rat model was built. CRNDE was obviously increased in CCI rats. Interestingly, overexpression of CRNDE enhanced neuropathic pain behaviors. Neuroinflammation was induced by CRNDE and as demonstrated, interleukin-10 (IL-10), IL-1, IL-6, and tumor necrosis factor-α (TNF-α) protein levels in CCI rats were activated by LV-CRNDE. For another, miR-136 was obviously reduced in CCI rats. Previously, it is indicated that miR-136 participates in the spinal cord injury via an inflammation in a rat model. Here, firstly, we verified miR-136 could serve as CRNDE target. Loss of miR-136 triggered neuropathic pain remarkably via the neuroinflammation activation. Additionally, IL6R was indicated as a target of miR-136 and miR-136 regulated its expression. Subsequently, we confirmed that CRNDE could induce interleukin 6 receptor (IL6R) expression positively. Overall, it was implied that CRNDE promoted neuropathic pain progression via modulating miR-136/IL6R axis in CCI rat models.
神经病理性疼痛已被报道为一种由于躯体感觉神经系统的主要功能障碍引起的慢性疼痛。它是最严重的慢性疼痛类型，可导致严重的公共健康负担。但是，对神经病理性疼痛的细胞和分子发病机制的理解还远远不够。长链非编码 RNA（lncRNA）最近被认为是神经元功能的调节剂。越来越多的研究表明，lncRNA 可以在神经病理性疼痛的发展中发挥重要作用。因此，我们目前的研究集中在 lncRNA 结直肠肿瘤差异表达（CRNDE）在神经病理性疼痛进展中的潜在作用。首先，建立了慢性缩窄性损伤（CCI）大鼠模型。CRNDE 在 CCI 大鼠中明显增加。有趣的是，CRNDE 的过表达增强了神经病理性疼痛行为。CRNDE 诱导神经炎症，并且如所证明的，CCI 大鼠中的白细胞介素 10（IL-10）、IL-1、IL-6 和肿瘤坏死因子-α（TNF-α）蛋白水平被 LV-CRNDE 激活。另一方面，miR-136 在 CCI 大鼠中明显减少。先前，已经表明 miR-136 通过大鼠模型中的炎症参与脊髓损伤。在这里，首先，我们验证了 miR-136 可以作为 CRNDE 的靶点。miR-136 的缺失通过神经炎症的激活显著引发神经病理性疼痛。此外，IL6R 被指示为 miR-136 的靶标，并且 miR-136 调节其表达。随后，我们证实 CRNDE 可以正向诱导白细胞介素 6 受体（IL6R）的表达。总的来说，在 CCI 大鼠模型中，CRNDE 通过调节 miR-136/IL6R 轴促进神经病理性疼痛的进展。
Zotero 插件