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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| Format: | Article |
| Language: | English |
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De Gruyter
2016-01-01
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| Series: | Translational Neuroscience |
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| Online Access: | https://doi.org/10.1515/tnsci-2016-0008 |
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| author | Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai |
| author_facet | Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai |
| author_sort | Wang Xiaoping |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T21:17:06Z |
| format | Article |
| id | doaj.art-5583841c648a4ac6bc5740f06e939308 |
| institution | Directory Open Access Journal |
| issn | 2081-6936 |
| language | English |
| last_indexed | 2024-12-20T21:17:06Z |
| publishDate | 2016-01-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Translational Neuroscience |
| spelling | doaj.art-5583841c648a4ac6bc5740f06e9393082022-12-21T19:26:23ZengDe GruyterTranslational Neuroscience2081-69362016-01-0171505510.1515/tnsci-2016-0008tnsci-2016-0008Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injuryWang Xiaoping0Li Xiaojia1Huang Bin2Ma Shuai3Department of Neurology Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital Chengdu,Sichuan 610072, P.R. ChinaDepartment of Neurology Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital Chengdu,Sichuan 610072, P.R. ChinaDepartment of Neurology Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital Chengdu,Sichuan 610072, P.R. ChinaDepartment of Neurology Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital Chengdu,Sichuan 610072, P.R. ChinaSpinal 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.https://doi.org/10.1515/tnsci-2016-0008mammalian target of rapamycin (mtor) protein kinaseneuropathic painspinal cord injury |
| spellingShingle | Wang Xiaoping Li Xiaojia Huang Bin Ma Shuai Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury Translational Neuroscience mammalian target of rapamycin (mtor) protein kinase neuropathic pain spinal cord injury |
| title | 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_short | 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 |
| topic | mammalian target of rapamycin (mtor) protein kinase neuropathic pain spinal cord injury |
| url | https://doi.org/10.1515/tnsci-2016-0008 |
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