PMID- 29587559
OWN - NLM
STAT- MEDLINE
DCOM- 20181022
LR  - 20220318
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 14
DP  - 2018 Jan-Dec
TI  - Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin 
      on oxaliplatin-induced neuropathic pain.
PG  - 1744806918769426
LID - 10.1177/1744806918769426 [doi]
LID - 1744806918769426
AB  - Background Oxaliplatin is a third-generation chemotherapeutic agent that is 
      commonly used to treat metastatic digestive tumors; however, one of the main 
      limiting complications of oxaliplatin is painful peripheral neuropathy. The 
      purpose of this study was to examine the underlying mechanisms by which mammalian 
      target of rapamycin (mTOR) and its signal are responsible for oxaliplatin-evoked 
      neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal 
      injection of oxaliplatin in rats. ELISA and Western blot analysis were used to 
      examine the levels of pro-inflammatory cytokines (including interleukin (IL)-1beta, 
      IL-6, and tumor necrosis factor (TNF)-alpha) and the expression of mTOR signal 
      pathway. Results Oxaliplatin increased mechanical and cold sensitivity as 
      compared with control animals ( P < 0.05 vs. control rats). Oxaliplatin also 
      amplified the expression of p-mTOR and mTOR-mediated phosphorylation of p70 
      ribosomal S6 protein kinase 1 and 4E-binding protein 1 in the lumbar dorsal root 
      ganglion. Blocking mTOR using rapamycin attenuated peripheral painful neuropathy 
      observed in oxaliplatin rats ( P < 0.05 vs. vehicle control). This inhibitory 
      effect was accompanied with decreases of IL-1beta, IL-6, and TNF-alpha. In addition, 
      inhibition of phosphatidylinositide 3-kinase (p-PI3K) attenuated the expression 
      of p-mTOR and the levels of pro-inflammatory cytokines in oxaliplatin rats, and 
      this further attenuated mechanical and cold hypersensitivity. Conclusions The 
      data revealed specific signaling pathways leading to oxaliplatin-induced 
      peripheral neuropathic pain, including the activation of PI3K-mTOR and 
      pro-inflammatory cytokine signal. Inhibition of these pathways alleviates 
      neuropathic pain. Targeting one or more of these molecular mediators may present 
      new opportunities for treatment and management of neuropathic pain observed 
      during chemotherapeutic application of oxaliplatin.
FAU - Duan, Zongsheng
AU  - Duan Z
AD  - 1 Department of Anesthesiology, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Su, Zhenbo
AU  - Su Z
AD  - 2 Department of Anesthesiology, China-Japan Union Hospital of Jilin University, 
      Changchun, China.
FAU - Wang, Hushan
AU  - Wang H
AD  - 1 Department of Anesthesiology, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Pang, Xiaochuan
AU  - Pang X
AD  - 3 Clinical Laboratory, The First Hospital of Jilin University, Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20180327
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Organoplatinum Compounds)
RN  - 04ZR38536J (Oxaliplatin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - Cold Hypersensitivity
SB  - IM
MH  - Animals
MH  - Cryopyrin-Associated Periodic Syndromes/drug therapy/metabolism/pathology
MH  - Cytokines/metabolism
MH  - Inflammation/*metabolism/*pathology
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Neuralgia/*drug therapy/metabolism/*pathology
MH  - Organoplatinum Compounds/*adverse effects
MH  - Oxaliplatin
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats, Sprague-Dawley
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
PMC - PMC5898663
OTO - NOTNLM
OT  - Oxaliplatin
OT  - mTOR
OT  - neuropathic pain
OT  - pro-inflammation
OT  - rapamycin
EDAT- 2018/03/29 06:00
MHDA- 2018/10/23 06:00
PMCR- 2018/03/27
CRDT- 2018/03/29 06:00
PHST- 2018/03/29 06:00 [pubmed]
PHST- 2018/10/23 06:00 [medline]
PHST- 2018/03/29 06:00 [entrez]
PHST- 2018/03/27 00:00 [pmc-release]
AID - 10.1177_1744806918769426 [pii]
AID - 10.1177/1744806918769426 [doi]
PST - ppublish
SO  - Mol Pain. 2018 Jan-Dec;14:1744806918769426. doi: 10.1177/1744806918769426. Epub 
      2018 Mar 27.