PMID- 30560396
OWN - NLM
STAT- MEDLINE
DCOM- 20190507
LR  - 20211204
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 44
IP  - 2
DP  - 2019 Feb
TI  - Suberoylanilide Hydroxamic Acid Triggers Autophagy by Influencing the mTOR 
      Pathway in the Spinal Dorsal Horn in a Rat Neuropathic Pain Model.
PG  - 450-464
LID - 10.1007/s11064-018-2698-1 [doi]
AB  - Histone acetylation levels can be upregulated by treating cells with histone 
      deacetylase inhibitors (HDACIs), which can induce autophagy. Autophagy flux in 
      the spinal cord of rats following the left fifth lumber spinal nerve ligation 
      (SNL) is involved in the progression of neuropathic pain. Suberoylanilide 
      hydroxamic acid (SAHA), one of the HDACIs can interfere with the epigenetic 
      process of histone acetylation, which has been shown to ease neuropathic pain. 
      Recent research suggest that SAHA can stimulate autophagy via the mammalian 
      target of rapamycin (mTOR) pathway in some types of cancer cells. However, little 
      is known about the role of SAHA and autophagy in neuropathic pain after nerve 
      injury. In the present study, we aim to investigate autophagy flux and the role 
      of the mTOR pathway on spinal cells autophagy activation in neuropathic pain 
      induced by SNL in rats that received SAHA treatment. Autophagy-related proteins 
      and mTOR or its active form were assessed by using western blot, 
      immunohistochemistry, double immunofluorescence staining and transmission 
      electron microscopy (TEM). We found that SAHA decreased the paw mechanical 
      withdrawal threshold (PMWT) of the lower compared with SNL. Autophagy flux was 
      mainly disrupted in the astrocytes and neuronal cells of the spinal cord dorsal 
      horn on postsurgical day 28 and was reversed by daily intrathecal injection of 
      SAHA (n = 100 nmol/day or n = 200 nmol/day). SAHA also decreased mTOR and 
      phosphorylated mTOR (p-mTOR) expression, especially p-mTOR expression in 
      astrocytes and neuronal cells of the spinal dorsal horn. These results suggest 
      that SAHA attenuates neuropathic pain and contributes to autophagy flux in 
      astrocytes and neuronal cells of the spinal dorsal horn via the mTOR signaling 
      pathway.
FAU - Feng, Xiang-Lan
AU  - Feng XL
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China.
FAU - Deng, Hong-Bo
AU  - Deng HB
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China.
FAU - Wang, Zheng-Gang
AU  - Wang ZG
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China.
FAU - Wu, Yun
AU  - Wu Y
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China.
FAU - Ke, Jian-Juan
AU  - Ke JJ
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China.
FAU - Feng, Xiao-Bo
AU  - Feng XB
AUID- ORCID: 0000-0002-3065-7949
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, No. 169 
      Donghu Rd, Wuhan, 430071, Hubei, China. lananesthesia@sina.com.
LA  - eng
GR  - 81471858/National Natural Science Foundation of China/
GR  - WJ2017M036/Hubei Provincial Population and Family Planning Commission/
PT  - Journal Article
DEP - 20181217
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 58IFB293JI (Vorinostat)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Autophagy/*drug effects
MH  - Disease Models, Animal
MH  - Histone Deacetylase Inhibitors/metabolism/pharmacology
MH  - Male
MH  - Neuralgia/*drug therapy/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Spinal Cord Dorsal Horn/drug effects/metabolism
MH  - Spinal Nerves/drug effects/injuries
MH  - TOR Serine-Threonine Kinases/*drug effects
MH  - Vorinostat/*pharmacology
OTO - NOTNLM
OT  - Autophagy flux
OT  - Histone deacetylase inhibitor
OT  - Mammalian target of rapamycin
OT  - Neuropathic pain
OT  - Spinal dorsal horn
EDAT- 2018/12/19 06:00
MHDA- 2019/05/08 06:00
CRDT- 2018/12/19 06:00
PHST- 2018/07/28 00:00 [received]
PHST- 2018/12/10 00:00 [accepted]
PHST- 2018/11/05 00:00 [revised]
PHST- 2018/12/19 06:00 [pubmed]
PHST- 2019/05/08 06:00 [medline]
PHST- 2018/12/19 06:00 [entrez]
AID - 10.1007/s11064-018-2698-1 [pii]
AID - 10.1007/s11064-018-2698-1 [doi]
PST - ppublish
SO  - Neurochem Res. 2019 Feb;44(2):450-464. doi: 10.1007/s11064-018-2698-1. Epub 2018 
      Dec 17.