Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441021, P.R. China.
Mol Med Rep. 2022 Jul;26(1). doi: 10.3892/mmr.2022.12737. Epub 2022 May 18.
Neuropathic pain (NP) is one of the most intractable diseases. The lack of effective therapeutic measures remains a major problem due to the poor understanding of the cause of NP. The aim of the present study was to investigate the effect of the long non‑coding RNA small nucleolar RNA host gene 5 (SNHG5) in NP and the underlying molecular mechanism in order to identify possible therapeutic targets. A chronic constriction injury (CCI) mouse model was used to investigate whether SNHG5 prevents NP and the inflammatory response. Luciferase and RNA pull‑down assays were used to detect the binding between SNHG5 and miR‑142‑5p as well as between miR‑142‑5p and CAMK2A. Western blot and qPCR were used to detect the RNA and protein expression. The results indicated that SNHG5 significantly inhibited CCI‑induced NP. In addition, SNHG5 inhibited the inflammatory response through decreasing the release and the mRNA expression of interleukin (IL)‑1β, IL‑6, IL‑10 and tumor necrosis factor‑α. Mechanistically, SNHG5 acted via sponging microRNA‑142‑5p, thereby upregulating the expression of calcium/calmodulin‑dependent protein kinase II α (CAMK2A). Further investigation indicated that CAMK2A knockdown also inhibited CCI‑induced NP and inflammation. In summary, the present study demonstrated that SNHG5 silencing could alleviate the neuropathic pain induced by chronic constriction injury via sponging miR‑142‑5p and regulating the expression of CAMK2A.
神经病理性疼痛(NP)是一种最棘手的疾病之一。由于对 NP 病因的了解不足,缺乏有效的治疗措施仍然是一个主要问题。本研究旨在探讨长链非编码 RNA 小核仁 RNA 宿主基因 5(SNHG5)在 NP 中的作用及其潜在的分子机制,以确定可能的治疗靶点。采用慢性缩窄性损伤(CCI)小鼠模型研究 SNHG5 是否可预防 NP 和炎症反应。荧光素酶和 RNA 下拉实验用于检测 SNHG5 与 miR-142-5p 以及 miR-142-5p 与 CAMK2A 之间的结合。Western blot 和 qPCR 用于检测 RNA 和蛋白质表达。结果表明,SNHG5 可显著抑制 CCI 诱导的 NP。此外,SNHG5 通过减少白细胞介素(IL)-1β、IL-6、IL-10 和肿瘤坏死因子-α的释放和 mRNA 表达来抑制炎症反应。机制上,SNHG5 通过海绵吸附 microRNA-142-5p ,从而上调钙/钙调蛋白依赖性蛋白激酶 2A(CAMK2A)的表达。进一步研究表明,CAMK2A 敲低也可抑制 CCI 诱导的 NP 和炎症。综上所述,本研究表明,沉默 SNHG5 可通过海绵吸附 miR-142-5p 并调节 CAMK2A 的表达来缓解慢性缩窄性损伤引起的神经病理性疼痛。