PMID- 32061737
OWN - NLM
STAT- MEDLINE
DCOM- 20210729
LR  - 20211204
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1733
DP  - 2020 Apr 15
TI  - Effects of mTOR inhibitors on neuropathic pain revealed by optical imaging of the 
      insular cortex in rats.
PG  - 146720
LID - S0006-8993(20)30076-7 [pii]
LID - 10.1016/j.brainres.2020.146720 [doi]
AB  - In the pain matrix, the insular cortex (IC) is mainly involved in discriminative 
      sensory and motivative emotion. Abnormal signal transmission from injury site 
      causes neuropathic pain, which generates enhanced synaptic plasticity. The 
      mammalian target of rapamycin (mTOR) complex is the key regulator of protein 
      synthesis; it is involved in the modulation of synaptic plasticity. To date, 
      there has been no report on the changes in optical signals in the IC under 
      neuropathic condition after treatment with mTOR inhibitors, such as Torin1 and 
      XL388. Therefore, we aimed to determine the pain-relieving effect of mTOR 
      inhibitors (Torin1 and XL388) and observe the changes in optical signals in the 
      IC after treatment. Mechanical threshold was measured in adult male 
      Sprague-Dawley rats after neuropathic surgery, and therapeutic effect of 
      inhibitors was assessed on post-operative day 7 following the microinjection of 
      Torin1 or XL388 into the IC. Optical signals were acquired to observe the 
      neuronal activity of the IC in response to peripheral stimulation before and 
      after treatment with mTOR inhibitors. Consequently, the inhibitors showed the 
      most effective alleviation 4 h after microinjection into the IC. In optical 
      imaging, peak amplitudes of optical signals and areas of activated regions were 
      reduced after treatment with Torin1 and XL388. However, there were no significant 
      optical signal changes in the IC before and after vehicle application. These 
      findings suggested that Torin1 and XL388 are associated with the alleviation of 
      neuronal activity that is excessively manifested in the IC, and is assumed to 
      diminish synaptic plasticity.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Kim, Kyeongmin
AU  - Kim K
AD  - Department of Physiology, Yonsei University College of Medicine, Seoul 03722, 
      Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei 
      University College of Medicine, Seoul 03722, Republic of Korea.
FAU - Choi, Songyeon
AU  - Choi S
AD  - Department of Physiology, Yonsei University College of Medicine, Seoul 03722, 
      Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei 
      University College of Medicine, Seoul 03722, Republic of Korea.
FAU - Cha, Myeounghoon
AU  - Cha M
AD  - Department of Physiology, Yonsei University College of Medicine, Seoul 03722, 
      Republic of Korea.
FAU - Lee, Bae Hwan
AU  - Lee BH
AD  - Department of Physiology, Yonsei University College of Medicine, Seoul 03722, 
      Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei 
      University College of Medicine, Seoul 03722, Republic of Korea. Electronic 
      address: bhlee@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200214
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 
      (1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one)
RN  - 0 (Naphthyridines)
RN  - 0 (Sulfones)
RN  - 0 (XL388)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/*drug effects/*metabolism
MH  - Male
MH  - Naphthyridines/*administration & dosage
MH  - Neuralgia/*metabolism
MH  - Optical Imaging
MH  - Pain Threshold/drug effects
MH  - Rats, Sprague-Dawley
MH  - Sulfones/*administration & dosage
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Cortical activity
OT  - Neuropathic pain
OT  - Optical imaging
OT  - insular cortex (IC)
OT  - mTOR complex
EDAT- 2020/02/18 06:00
MHDA- 2021/07/30 06:00
CRDT- 2020/02/17 06:00
PHST- 2019/08/29 00:00 [received]
PHST- 2020/01/22 00:00 [revised]
PHST- 2020/02/07 00:00 [accepted]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2021/07/30 06:00 [medline]
PHST- 2020/02/17 06:00 [entrez]
AID - S0006-8993(20)30076-7 [pii]
AID - 10.1016/j.brainres.2020.146720 [doi]
PST - ppublish
SO  - Brain Res. 2020 Apr 15;1733:146720. doi: 10.1016/j.brainres.2020.146720. Epub 
      2020 Feb 14.