Hyperbaric oxygen relieves neuropathic pain through AKT/TSC2/mTOR pathway activity to induce autophagy
Received 8 October 2018
Accepted for publication 7 December 2018
Published 23 January 2019 Volume 2019:12 Pages 443—451
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr E Alfonso Romero-Sandoval
Yong-Da Liu,1 Zhi-Bin Wang,1 Guang Han,1 Li Jin,2 Ping Zhao1
1Department of Anesthesiology and Pain Management, Shengjing Hospital of China Medical University, Shenyang 110004, China; 2Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USA
Background: Our previous study suggested that HBO treatment attenuated neuropathic pain by inhibiting mTOR to induce autophagy in SNL neuropathic pain model. The aim of this study was to evaluate the role of AKT/TSC2/mTOR pathway in SNL and autophagy and determine whether HBO treatment could relieve neuropathic pain via modulating AKT/TSC2/mTOR pathway.
Materials and methods: Rats were randomly divided into sham, SNL, SNL + HBO treatment, SNL + vehicle, and SNL + AKT inhibitor groups. Neuropathic pain was induced following SNL procedure. Rats in the SNL + HBO group received HBO treatment for 7 consecutive days beginning on postoperative day 1. The SNL + vehicle group received 10 µL of 3% dimethyl sulfoxide in saline. SNL + AKT inhibitor group received 10 µL AKT inhibitor IV intrathecally. Mechanical withdrawal threshold tests were performed to evaluate mechanical hypersensitivity. AKT, p-AKT, TSC2, mTOR, p-mTOR, and LC3-II protein expressions were examined by Western blot analysis.
Results: HBO reversed AKT/TSC2/mTOR upregulation induced by SNL and attenuated neuropathic pain. Intrathecal injection of AKT inhibitor IV decreased the activity of AKT/TSC2/mTOR pathway and increased LC3-II expression accompanied by analgesic effect in SNL rats.
Conclusion: Taken together, our findings demonstrated AKT/TSC2/mTOR pathway was activated in SNL-induced neuropathic pain, and HBO treatment attenuated neuropathic pain via neutralizing AKT/TSC2/mTOR pathway activation.
Keywords: neuropathic pain, autophagy, mTOR, TSC2, AKT, hyperbaric oxygen
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