Department of Anesthesiology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China.
Department of Anesthesiology, The Seventh Medical Center of PLA General Hospital, Beijing 100700, China.
Can J Physiol Pharmacol. 2020 Dec;98(12):870-877. doi: 10.1139/cjpp-2020-0036. Epub 2020 Dec 2.
Neuropathic pain is a type of spontaneous pain that causes damage to the central nervous system. Long noncoding RNAs (lncRNAs) participate in the progression of various nervous system diseases, including neuropathic pain. However, the biological function of GAS5 in neuropathic pain remains unclear. Our findings revealed that GAS5 was downregulated in chronic constriction injury (CCI) rats. Besides, ELISA showed that the concentration of IL-6, TNF-α, and IL-1β were reduced by overexpressed GAS5 in spinal cord homogenates of CCI rats. Moreover, mechanical allodynia and thermal hyperalgesia in CCI rats were inhibited by GAS5 overexpression, suggesting that GAS5 overexpression attenuated neuropathic pain. Subsequently, we found that GAS5 served as a sponge for miR-452-5p in CCI rats and CELF2 was the downstream target of miR-452-5p. Finally, through a rescue assay, we found that GAS5 ameliorated neuropathic pain in CCI rats by sponging miR-452-5p to regulate CELF2 expression. Our study confirmed that GAS5 ameliorated neuropathic pain in rats by modulation of the miR-452-5p/CELF2 axis, which may provide some clues for neuropathic pain treatment.
神经病理性疼痛是一种自发性疼痛，可导致中枢神经系统损伤。长链非编码 RNA（lncRNA）参与多种神经系统疾病的进展，包括神经病理性疼痛。然而，GAS5 在神经病理性疼痛中的生物学功能尚不清楚。我们的研究结果表明，GAS5 在慢性压迫损伤（CCI）大鼠中表达下调。此外，ELISA 显示，过表达 GAS5 可降低 CCI 大鼠脊髓匀浆中 IL-6、TNF-α 和 IL-1β 的浓度。此外，GAS5 的过表达抑制 CCI 大鼠的机械性痛觉过敏和热痛觉过敏，表明 GAS5 的过表达可减轻神经病理性疼痛。随后，我们发现 GAS5 在 CCI 大鼠中作为 miR-452-5p 的海绵体，CELF2 是 miR-452-5p 的下游靶标。最后，通过挽救试验，我们发现 GAS5 通过海绵 miR-452-5p 来调节 CELF2 表达，从而改善 CCI 大鼠的神经病理性疼痛。我们的研究证实，GAS5 通过调节 miR-452-5p/CELF2 轴改善大鼠的神经病理性疼痛，这可能为神经病理性疼痛的治疗提供一些线索。
