Xu Meijie, Wu Rui, Zhang Ling, Zhu Hong-Yan, Xu Guang-Yin, Qian Wenxia, Zhang Ping-An
Department of Respiratory and Critical Care Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, People's Republic of China.
Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China.
J Pain Res. 2020 Nov 19;13:3013-3022. doi: 10.2147/JPR.S279902. eCollection 2020.
Inflammatory pain is the most common type of pain treated clinically. However, the currently available treatments for inflammatory pain have limited effects and can cause severe side effects. The aim of this study is to describe the effect of miRNA-485-5p on osteoarthritis-related inflammatory pain.
Paw withdrawal threshold (PWT) of rats was measured by von Frey filaments. The expressions of miRNA-485-5p and acid-sensing ion channel 1 (ASIC1) in the dorsal root ganglion (DRG) were measured with real-time quantitative PCR and Western blotting analysis. Fluorescent in situ hybridization and fluorescent immunohistochemistry were employed to detect expression of miRNA-485-5p, acid-sensing ion channelASIC1 and co-location of miRNA-485-5p with ASIC1.
The PWT of rats was significantly reduced after complete Freund's adjuvant (CFA) injection. The miRNA-485-5p expression level clearly decreased while the ASIC1 expression level was upregulated in the L4-6 dorsal root ganglion (DRG) of CFA rats. MiRNA-485-5p and ASIC1 were co-expressed in the same DRG cells of CFA rats. Amiloride, an inhibitor of ASIC1, clearly increased the PWT of CFA rats. Further, miRNA-485-5p agomir reversed the upregulation of ASICI1 and alleviated CFA-induced mechanical hypersensitivity of CFA rats.
These results suggest that reduced expression of miRNA-485-5p contributes to inflammatory pain through upregulating ASIC1 expression, implying a promising strategy for pain therapy.
炎性疼痛是临床上最常见的疼痛类型。然而，目前用于治疗炎性疼痛的方法效果有限，且会引起严重的副作用。本研究旨在描述miRNA-485-5p对骨关节炎相关炎性疼痛的影响。
用von Frey细丝测量大鼠的 paw withdrawal threshold（PWT）。采用实时定量PCR和蛋白质免疫印迹分析检测背根神经节（DRG）中miRNA-485-5p和酸敏感离子通道1（ASIC1）的表达。采用荧光原位杂交和荧光免疫组织化学检测miRNA-485-5p、酸敏感离子通道ASIC1的表达以及miRNA-485-5p与ASIC1的共定位。
完全弗氏佐剂（CFA）注射后，大鼠的PWT显著降低。CFA大鼠L4-6背根神经节（DRG）中miRNA-485-5p表达水平明显降低，而ASIC1表达水平上调。miRNA-485-5p和ASIC1在CFA大鼠的同一DRG细胞中共表达。ASIC1抑制剂amiloride明显提高了CFA大鼠的PWT。此外，miRNA-485-5p激动剂逆转了ASIC1的上调，并减轻了CFA诱导的CFA大鼠机械性超敏反应。
这些结果表明，miRNA-485-5p表达降低通过上调ASIC1表达导致炎性疼痛增加，这意味着一种有前景的疼痛治疗策略。
