PMID- 30940563 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20211204 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 409 DP - 2019 Jun 15 TI - Alterations in the BDNF-mTOR Signaling Pathway in the Spinal Cord Contribute to Hyperalgesia in a Rodent Model of Chronic Restraint Stress. PG - 142-151 LID - S0306-4522(19)30214-3 [pii] LID - 10.1016/j.neuroscience.2019.03.052 [doi] AB - Stress is a non-specific, systemic, physiological response of the body to strong internal and external environmental stimuli. Accumulating evidence has suggested that stress, particularly chronic restraint stress (CRS), can reduce pain threshold and increase pain sensitivity. However, pathogenic and therapeutic mechanisms underlying CRS remain unclear. Here, we aimed to investigate roles of the brain-derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling pathway in CRS-induced abnormal pain sensitivity. CRS was successfully mimicked 7 days after model development, and paw withdrawal mechanical threshold (PWMT) and tail-flick latency (TFL) were evaluated. CRS significantly altered BDNF and mTOR phosphorylation in the anterior cingulate cortex and spinal cord but not in the hippocampus. On day 7, a single dose of 7,8-dihydroxyflavone, an activator of BDNF-tropomyosin receptor kinase B, was administered via intraperitoneal or intrathecal injection. Notably, only the intrathecal injection improved PWMT and TFL. Additionally, an intraperitoneal injection of rapamycin, an mTOR inhibitor, failed to induce any behavioral changes, whereas a single intrathecal injection of rapamycin improved abnormal CRS-induced PWMT and TFL. In conclusion, CRS can induce abnormal pain sensitivity, probably by altering the BDNF-mTOR signaling pathway in the spinal cord. CI - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Huang, Niannian AU - Huang N AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yang, Chun AU - Yang C AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Hua, Dongyu AU - Hua D AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Shan AU - Li S AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhan, Gaofeng AU - Zhan G AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yang, Ning AU - Yang N AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Luo, Ailin AU - Luo A AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Hui AU - Xu H AD - Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 844728147@qq.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190330 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Hyperalgesia/*metabolism MH - Male MH - Mice MH - Pain Measurement MH - Pain Threshold/physiology MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Restraint, Physical MH - Signal Transduction/*physiology MH - Spinal Cord/*metabolism MH - Stress, Psychological/*metabolism MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - brain-derived neurotrophic factor OT - chronic restraint stress OT - mammalian target of rapamycin OT - pain sensitivity OT - spinal cord EDAT- 2019/04/04 06:00 MHDA- 2020/01/10 06:00 CRDT- 2019/04/04 06:00 PHST- 2018/10/20 00:00 [received] PHST- 2019/03/23 00:00 [revised] PHST- 2019/03/26 00:00 [accepted] PHST- 2019/04/04 06:00 [pubmed] PHST- 2020/01/10 06:00 [medline] PHST- 2019/04/04 06:00 [entrez] AID - S0306-4522(19)30214-3 [pii] AID - 10.1016/j.neuroscience.2019.03.052 [doi] PST - ppublish SO - Neuroscience. 2019 Jun 15;409:142-151. doi: 10.1016/j.neuroscience.2019.03.052. Epub 2019 Mar 30.