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

Authors
J Shia, K Jiang, Z Li

Lab
Department of Anesthesiology, Guizhou Provincial People’s Hospital, China

Journal
Nueroscience Research

Abstract
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)-_, interleukin (IL)-1_ 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-_, IL-1_ and IL-6. We confirmed that miR-145 directly targeted Akt3, inhibiting NF-_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-_B signaling pathways.

BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)