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Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats

The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contrib...

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Autores principales: Um, Sun Woo, Kim, Min Jee, Leem, Joong Woo, Bai, Sun Joon, Lee, Bae Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459802/
https://www.ncbi.nlm.nih.gov/pubmed/30032425
http://dx.doi.org/10.1007/s12035-018-1245-z
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author Um, Sun Woo
Kim, Min Jee
Leem, Joong Woo
Bai, Sun Joon
Lee, Bae Hwan
author_facet Um, Sun Woo
Kim, Min Jee
Leem, Joong Woo
Bai, Sun Joon
Lee, Bae Hwan
author_sort Um, Sun Woo
collection PubMed
description The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions. Until now, there have been no reports that studied the role of mTOR signaling in the ACC involved in neuropathic pain. Therefore, this study was conducted to determine the relationship of mTOR signaling in the ACC and neuropathic pain. Male Sprague-Dawley rats were subjected to cannula implantation and nerve injury under pentobarbital anesthesia. Microinjection with rapamycin into the ACC was conducted under isoflurane anesthesia on postoperative day (POD) 7. A behavioral test was performed to evaluate mechanical allodynia, and optical imaging was conducted to observe the neuronal responses of the ACC to peripheral stimulation. Inhibition of mTOR by rapamycin reduced mechanical allodynia, down-regulated mTOR signaling in the ACC, and diminished the expressions of synaptic proteins which are involved in excitatory signaling, thereby reducing neuropathic pain-induced synaptic plasticity. These results suggest that inhibiting mTOR activity by rapamycin in the ACC could serve as a new strategy for treating or managing neuropathic pain before it develops into chronic pain.
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spelling pubmed-64598022019-05-03 Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats Um, Sun Woo Kim, Min Jee Leem, Joong Woo Bai, Sun Joon Lee, Bae Hwan Mol Neurobiol Article The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions. Until now, there have been no reports that studied the role of mTOR signaling in the ACC involved in neuropathic pain. Therefore, this study was conducted to determine the relationship of mTOR signaling in the ACC and neuropathic pain. Male Sprague-Dawley rats were subjected to cannula implantation and nerve injury under pentobarbital anesthesia. Microinjection with rapamycin into the ACC was conducted under isoflurane anesthesia on postoperative day (POD) 7. A behavioral test was performed to evaluate mechanical allodynia, and optical imaging was conducted to observe the neuronal responses of the ACC to peripheral stimulation. Inhibition of mTOR by rapamycin reduced mechanical allodynia, down-regulated mTOR signaling in the ACC, and diminished the expressions of synaptic proteins which are involved in excitatory signaling, thereby reducing neuropathic pain-induced synaptic plasticity. These results suggest that inhibiting mTOR activity by rapamycin in the ACC could serve as a new strategy for treating or managing neuropathic pain before it develops into chronic pain. Springer US 2018-07-22 2019 /pmc/articles/PMC6459802/ /pubmed/30032425 http://dx.doi.org/10.1007/s12035-018-1245-z Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Um, Sun Woo
Kim, Min Jee
Leem, Joong Woo
Bai, Sun Joon
Lee, Bae Hwan
Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title_full Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title_fullStr Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title_full_unstemmed Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title_short Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats
title_sort pain-relieving effects of mtor inhibitor in the anterior cingulate cortex of neuropathic rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459802/
https://www.ncbi.nlm.nih.gov/pubmed/30032425
http://dx.doi.org/10.1007/s12035-018-1245-z
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