Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain o...

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Autores principales:	Wang Xiaoping, Li Xiaojia, Huang Bin, Ma Shuai
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2016
Materias:	mammalian target of rapamycin (mtor) protein kinase neuropathic pain spinal cord injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5583841c648a4ac6bc5740f06e939308
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spelling	oai:doaj.org-article:5583841c648a4ac6bc5740f06e9393082021-12-05T14:11:04ZBlocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury2081-693610.1515/tnsci-2016-0008https://doaj.org/article/5583841c648a4ac6bc5740f06e9393082016-01-01T00:00:00Zhttps://doi.org/10.1515/tnsci-2016-0008https://doaj.org/toc/2081-6936Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.Wang XiaopingLi XiaojiaHuang BinMa ShuaiDe Gruyterarticlemammalian target of rapamycin (mtor) protein kinaseneuropathic painspinal cord injuryNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Neuroscience, Vol 7, Iss 1, Pp 50-55 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	mammalian target of rapamycin (mtor) protein kinase neuropathic pain spinal cord injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	mammalian target of rapamycin (mtor) protein kinase neuropathic pain spinal cord injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
description	Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.
format	article
author	Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai
author_facet	Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai
author_sort	Wang Xiaoping
title	Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
title_short	Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
title_full	Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
title_fullStr	Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
title_full_unstemmed	Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury
title_sort	blocking mammalian target of rapamycin (mtor) improves neuropathic pain evoked by spinal cord injury
publisher	De Gruyter
publishDate	2016
url	https://doaj.org/article/5583841c648a4ac6bc5740f06e939308
work_keys_str_mv	AT wangxiaoping blockingmammaliantargetofrapamycinmtorimprovesneuropathicpainevokedbyspinalcordinjury AT lixiaojia blockingmammaliantargetofrapamycinmtorimprovesneuropathicpainevokedbyspinalcordinjury AT huangbin blockingmammaliantargetofrapamycinmtorimprovesneuropathicpainevokedbyspinalcordinjury AT mashuai blockingmammaliantargetofrapamycinmtorimprovesneuropathicpainevokedbyspinalcordinjury
_version_	1718371420999778304

Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury

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