PMID- 28123821
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220318
IS  - 2081-3856 (Print)
IS  - 2081-6936 (Electronic)
IS  - 2081-6936 (Linking)
VI  - 7
IP  - 1
DP  - 2016
TI  - Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by 
      spinal cord injury.
PG  - 50-55
LID - 10.1515/tnsci-2016-0008 [doi]
AB  - 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.
FAU - Wang, Xiaoping
AU  - Wang X
AD  - Department of Neurology Sichuan Academy of Medical Science and Sichuan Provincial 
      People's Hospital Chengdu, Sichuan 610072, P.R. China.
FAU - Li, Xiaojia
AU  - Li X
AD  - Department of Neurology Sichuan Academy of Medical Science and Sichuan Provincial 
      People's Hospital Chengdu, Sichuan 610072, P.R. China.
FAU - Huang, Bin
AU  - Huang B
AD  - Department of Neurology Sichuan Academy of Medical Science and Sichuan Provincial 
      People's Hospital Chengdu, Sichuan 610072, P.R. China.
FAU - Ma, Shuai
AU  - Ma S
AD  - Department of Neurology Sichuan Academy of Medical Science and Sichuan Provincial 
      People's Hospital Chengdu, Sichuan 610072, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160628
PL  - Germany
TA  - Transl Neurosci
JT  - Translational neuroscience
JID - 101550327
PMC - PMC5234518
OTO - NOTNLM
OT  - Mammalian target of rapamycin (mTOR) protein kinase
OT  - Neuropathic pain
OT  - Spinal cord injury
EDAT- 2017/01/27 06:00
MHDA- 2017/01/27 06:01
PMCR- 2016/06/28
CRDT- 2017/01/27 06:00
PHST- 2015/11/12 00:00 [received]
PHST- 2015/12/15 00:00 [accepted]
PHST- 2017/01/27 06:00 [entrez]
PHST- 2017/01/27 06:00 [pubmed]
PHST- 2017/01/27 06:01 [medline]
PHST- 2016/06/28 00:00 [pmc-release]
AID - tnsci-2016-0008 [pii]
AID - 10.1515/tnsci-2016-0008 [doi]
PST - epublish
SO  - Transl Neurosci. 2016 Jun 28;7(1):50-55. doi: 10.1515/tnsci-2016-0008. 
      eCollection 2016.