PMID- 27279283
OWN - NLM
STAT- MEDLINE
DCOM- 20170919
LR  - 20220408
IS  - 1554-527X (Electronic)
IS  - 0736-0266 (Linking)
VI  - 35
IP  - 1
DP  - 2017 Jan
TI  - Rapamycin suppresses microglial activation and reduces the development of 
      neuropathic pain after spinal cord injury.
PG  - 93-103
LID - 10.1002/jor.23328 [doi]
AB  - Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling 
      pathway, plays an important role in multiple cellular functions. Our previous 
      study showed rapamycin treatment in acute phase reduced the neural tissue damage 
      and locomotor impairment after spinal cord injury (SCI). However, there has been 
      no study to investigate the therapeutic effect of rapamycin on neuropathic pain 
      after SCI. In this study, we examined whether rapamycin reduces neuropathic pain 
      following SCI in mice. We used a mouse model of thoracic spinal cord contusion 
      injury, and divided the mice into the rapamycin-treated and the vehicle-treated 
      groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin 
      (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K 
      in the injured spinal cord that indicated inhibition of mTOR. The rapamycin 
      treatment significantly improved not only locomotor function, but also mechanical 
      and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical 
      analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly 
      decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in 
      the lumbar spinal cord was significantly attenuated by rapamycin treatment. 
      Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased 
      in the rapamycin-treated mice. These results indicated rapamycin administration 
      in acute phase to reduce secondary neural tissue damage can contribute to the 
      suppression of the microglial activation in the lumbar spinal cord and attenuate 
      the development of neuropathic pain after SCI. The present study first 
      demonstrated that rapamycin has significant therapeutic potential to reduce the 
      development of neuropathic pain following SCI. (c) 2016 Orthopaedic Research 
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017.
CI  - (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
FAU - Tateda, Satoshi
AU  - Tateda S
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Kanno, Haruo
AU  - Kanno H
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Ozawa, Hiroshi
AU  - Ozawa H
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Sekiguchi, Akira
AU  - Sekiguchi A
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Yahata, Kenichiro
AU  - Yahata K
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Yamaya, Seiji
AU  - Yamaya S
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
FAU - Itoi, Eiji
AU  - Itoi E
AD  - Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 
      1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160622
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Aif1 protein, mouse)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Microfilament Proteins)
RN  - 0 (glial fibrillary astrocytic protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/metabolism
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hyperalgesia/prevention & control
MH  - Locomotion/drug effects
MH  - Mice, Inbred C57BL
MH  - Microfilament Proteins/metabolism
MH  - Neuralgia/etiology/*prevention & control
MH  - Neuroglia/*drug effects/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Sirolimus/pharmacology/*therapeutic use
MH  - Spinal Cord Injuries/*complications/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - microglia
OT  - neuropathic pain
OT  - rapamycin
OT  - spinal cord injury
EDAT- 2016/06/10 06:00
MHDA- 2017/09/20 06:00
CRDT- 2016/06/10 06:00
PHST- 2016/01/05 00:00 [received]
PHST- 2016/06/05 00:00 [accepted]
PHST- 2016/06/10 06:00 [pubmed]
PHST- 2017/09/20 06:00 [medline]
PHST- 2016/06/10 06:00 [entrez]
AID - 10.1002/jor.23328 [doi]
PST - ppublish
SO  - J Orthop Res. 2017 Jan;35(1):93-103. doi: 10.1002/jor.23328. Epub 2016 Jun 22.