title: Inhibition of MicroRNA-221 Alleviates Neuropathic Pain Through Targeting Suppressor of Cytokine Signaling 1.
abstract: Neuropathic pain results in considerable trouble to people's physical and mental health. The pathophysiological mechanisms underlying its occurrence and development remain unclear. A large number of experiments show that microRNAs (miRNAs) play a major role in the pathogenesis of neuropathic pain and neuroinflammation resulting from nerve injury. Among various miRNAs, microRNA-221 (miR-221) overexpression has been reported in a chronic constrictive injury (CCI)-induced rat model of neuropathic pain. However, the role of miR-221 in the regulation of neuropathic pain is unknown. In this study, we investigated the potential role and underlying mechanism of miR-221 in regulating neuropathic pain. Our findings show that miR-221 is overexpressed in the spinal cord and the isolated microglia of CCI rats. Intrathecal injection of a miR-221 inhibitor attenuated CCI-induced mechanical allodynia and thermal hyperalgesia, and reduced proinflammatory cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in CCI rats. Using a dual-luciferase reporter assay, we show that suppressor of cytokine signaling 1 (SOCS1), an important regulator of inflammation, is a direct target of miR-221. Treatment with the miR-221 inhibitor significantly inhibited the expression of SOCS1. Furthermore, the miR-221 inhibitor markedly suppressed the activation of nuclear factor-kappa B (NF-κB) and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Knockdown of SOCS1 in CCI rats abrogated the inhibitory effect of the miR-221 inhibitor on CCI-induced neuropathic pain and the NF-κB and p38 MAPK signaling pathways. Together, these results suggest that inhibition of miR-221 alleviates neuropathic pain and neuroinflammation through increasing SOCS1 and by inhibiting the NF-κB and p38 MAPK signaling pathways, indicating that miR-221 may be a promising molecular target for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Jinshui District, Zhengzhou, 450014, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Maternal and Child Health Hospital of Zhengzhou, Zhengzhou, 450000, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Jinshui District, Zhengzhou, 450014, People's Republic of China. tielidong@163.com.
authors.forename: Tieli
authors.initials: T
authors.lastname: Dong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C576526:MIRN221 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; C491589:Socs1 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Inflammatory response; Neuropathic pain; Suppressor of cytokine signaling 1; miR-221