Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats

Abstract Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain m...

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Main Authors: Myeounghoon Cha, Songyeon Choi, Kyeongmin Kim, Bae Hwan Lee
Format: Article
Language:English
Published: BMC 2020-11-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-020-00687-1
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spelling doaj-b91aea9fc1274f82b0fd1045734665b82020-12-06T12:29:09ZengBMCMolecular Brain1756-66062020-11-0113111010.1186/s13041-020-00687-1Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain ratsMyeounghoon Cha0Songyeon Choi1Kyeongmin Kim2Bae Hwan Lee3Department of Physiology, Yonsei University College of MedicineDepartment of Physiology, Yonsei University College of MedicineDepartment of Physiology, Yonsei University College of MedicineDepartment of Physiology, Yonsei University College of MedicineAbstract Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.https://doi.org/10.1186/s13041-020-00687-1MEMRImTORChronic painTorin1XL388
collection DOAJ
language English
format Article
sources DOAJ
author Myeounghoon Cha
Songyeon Choi
Kyeongmin Kim
Bae Hwan Lee
spellingShingle Myeounghoon Cha
Songyeon Choi
Kyeongmin Kim
Bae Hwan Lee
Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
Molecular Brain
MEMRI
mTOR
Chronic pain
Torin1
XL388
author_facet Myeounghoon Cha
Songyeon Choi
Kyeongmin Kim
Bae Hwan Lee
author_sort Myeounghoon Cha
title Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
title_short Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
title_full Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
title_fullStr Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
title_full_unstemmed Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats
title_sort manganese-enhanced mri depicts a reduction in brain responses to nociception upon mtor inhibition in chronic pain rats
publisher BMC
series Molecular Brain
issn 1756-6606
publishDate 2020-11-01
description Abstract Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.
topic MEMRI
mTOR
Chronic pain
Torin1
XL388
url https://doi.org/10.1186/s13041-020-00687-1
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