MiR-145 ameliorates neuropathic pain via inhibiting inflammatory responses and mTOR signaling pathway by targeting Akt3 in a rat model

Neuropathic pain perplexes a large population of patients with various diseases. Inflammation plays a key role in the physiopathology of neuropathic pain. Anti-inflammatory can be a promising strategy to treat neuropathic pain. We generated a chronic constriction injury rat model to mimic neuropathic pain by ligating the left ischiadic nerves of rats. Then we performed intrathecal injection of miR-145 mimics to treat these rats for seven consecutive days. Pain behavior tests including mechanical allodynia and thermal hyperalgesia, pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 were analyzed. Quantitative polymerase chain reaction and immunoblotting were performed to detect the changes of signaling pathway after miR-145 mimic treatment. Targeting of Akt3 by miR-145 was studied by dual-luciferase reporter gene assays. MiR-145 mimics injection significantly mollified both mechanical allodynia and thermal hyperalgesia in rats, and down-regulated secretion of TNF-alpha, IL-1 beta and IL-6. We confirmed that miR-145 directly targeted Akt3, inhibiting NF-kappa B and mTOR downstream genes in rat dorsal root ganglia. MiR-145 can mollify neuropathic pain in a chronic constriction injury rat model by reducing inflammation and ion channel overexpression through Akt3/mTOR and Akt3/NF-kappa B signaling pathways. (C) 2017 Published by Elsevier Ireland Ltd.