PMID- 34145195
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20230929
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 32
IP  - 11
DP  - 2021 Aug 4
TI  - Mammalian target of rapamycin signaling pathway is involved in synaptic 
      plasticity of the spinal dorsal horn and neuropathic pain in rats by regulating 
      autophagy.
PG  - 925-935
LID - 10.1097/WNR.0000000000001684 [doi]
AB  - Unveiling the etiology and the underlying mechanism of neuropathic pain, a poorly 
      treated disease, is essential for the development of effective therapies. This 
      study aimed to explore the role of mammalian target of rapamycin (mTOR) signaling 
      in autophagy-mediated neuropathic pain. We established a spared nerve injury 
      (SNI) model in adult male SD rats by ligating the common peroneal nerve and 
      tibial, with the distal end cutoff. The paw withdrawal threshold (PWT) and 
      C/A-fiber evoked field potentials were determined by electrophysiologic tests at 
      day 0 (before operation), day 7 and day 14 postoperation, and SNI significantly 
      increased field potentials (P < 0.05). Immunohistochemistry and western blots 
      using spinal cord tissues showed that the expressions of GluR1, GluR2, Beclin-1, 
      p62, mTOR and 4EBP1 were significantly increased after SNI (all P < 0.05), 
      whereas the expressions of LC3 and LAMP2 were significantly decreased after SNI 
      (all P < 0.05). Rapamycin efficiently counteracted the effect of SNI and restored 
      the phenotypes to the level comparable to the sham control. In conclusion, 
      rapamycin inhibits C/A-fiber-mediated long-term potentiation in the SNI rat model 
      of neuropathic pain, which might be mediated by activation of autophagy signaling 
      and downregulation of GluRs expression.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Hu, Jijun
AU  - Hu J
AD  - Department of Anesthesiology, Hubei Tongcheng People's Hospital, Tongcheng.
FAU - Chen, Xueling
AU  - Chen X
AD  - Department of Anesthesiology, Wuhan Children Hospital, Wuhan, China.
FAU - Cheng, Jie
AU  - Cheng J
AD  - Department of Anesthesiology, Wuhan Children Hospital, Wuhan, China.
FAU - Kong, Fanli
AU  - Kong F
AD  - Department of Anesthesiology, Wuhan Children Hospital, Wuhan, China.
FAU - Xia, Hui
AU  - Xia H
AD  - Department of Anesthesiology, Wuhan Children Hospital, Wuhan, China.
FAU - Wu, Jiang
AU  - Wu J
AD  - Department of Anesthesiology, Wuhan Children Hospital, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Male
MH  - Neuralgia/drug therapy/*metabolism
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - Spinal Cord Dorsal Horn/drug effects/*metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
EDAT- 2021/06/20 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/06/19 05:41
PHST- 2021/06/20 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/06/19 05:41 [entrez]
AID - 00001756-202108010-00002 [pii]
AID - 10.1097/WNR.0000000000001684 [doi]
PST - ppublish
SO  - Neuroreport. 2021 Aug 4;32(11):925-935. doi: 10.1097/WNR.0000000000001684.