PMID- 26566757
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20211203
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 138
IP  - 8
DP  - 2016 Apr 15
TI  - Blocking mammalian target of rapamycin alleviates bone cancer pain and morphine 
      tolerance via micro-opioid receptor.
PG  - 2013-20
LID - 10.1002/ijc.29927 [doi]
AB  - The current study was to examine the underlying mechanisms responsible for the 
      role of mammalian target of rapamycin (mTOR) in regulating bone cancer-evoked 
      pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 
      cells were implanted into the tibia bone cavity of rats and this evoked 
      significant mechanical and thermal hyperalgesia. Our results showed that the 
      protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 
      4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) as well as 
      phosphatidylinositide 3-kinase (p-PI3K) pathways were amplified in the 
      superficial dorsal horn of the spinal cord of bone cancer rats compared with 
      control rats. Blocking spinal mTOR by using rapamycin significantly attenuated 
      activities of PI3K signaling pathways as well as mechanical and thermal 
      hyperalgesia. Additionally, rapamycin enhanced attenuations of protein kinase Cvarepsilon 
      (PKCvarepsilon)/protein kinase A (PKA) induced by morphine and further extended analgesia 
      of morphine via micro-opioid receptor (MOR). Our data for the first time revealed 
      specific signaling pathways leading to bone cancer pain, including the activation 
      of mTOR and PI3K and downstream PKCvarepsilon/PKA, and resultant sensitization of MOR. 
      Targeting one or more of these signaling molecules may present new opportunities 
      for treatment and management of bone cancer pain often observed in clinics.
CI  - (c) 2015 UICC.
FAU - Jiang, Zongming
AU  - Jiang Z
AD  - Department of Anesthesiology, Shaoxing People's Hospital (Shaoxing Hospital of 
      Zhejiang University), Shaoxing, Zhejiang, 312000, China.
FAU - Wu, Shaoyong
AU  - Wu S
AD  - Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangdong, 510000, China.
FAU - Wu, Xiujuan
AU  - Wu X
AD  - Department of Nephrology, Shaoxing People's Hospital (Shaoxing Hospital of 
      Zhejiang University), Shaoxing, Zhejiang, 312000, China.
FAU - Zhong, Junfeng
AU  - Zhong J
AD  - Department of Anesthesiology, Shaoxing People's Hospital (Shaoxing Hospital of 
      Zhejiang University), Shaoxing, Zhejiang, 312000, China.
FAU - Lv, Anqing
AU  - Lv A
AD  - Department of Anesthesiology, Shaoxing People's Hospital (Shaoxing Hospital of 
      Zhejiang University), Shaoxing, Zhejiang, 312000, China.
FAU - Jiao, Jing
AU  - Jiao J
AD  - Department of Anesthesiology, Shanghai Obstetrics and Gynecology Hospital, Fudan 
      University, Shanghai, 200011, China.
FAU - Chen, Zhonghua
AU  - Chen Z
AD  - Department of Anesthesiology, Shaoxing People's Hospital (Shaoxing Hospital of 
      Zhejiang University), Shaoxing, Zhejiang, 312000, China.
LA  - eng
PT  - Journal Article
DEP - 20151208
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Receptors, Opioid, mu)
RN  - 76I7G6D29C (Morphine)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Int J Cancer. 2016 Oct 1;139(7):1670-1. PMID: 27244273
CIN - Int J Cancer. 2016 Oct 1;139(7):1672. PMID: 27244694
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Bone Neoplasms/*complications
MH  - Disease Models, Animal
MH  - Drug Tolerance/*physiology
MH  - Morphine/pharmacology
MH  - Pain/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, mu/*metabolism
MH  - Signal Transduction/physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - bone cancer
OT  - mTOR
OT  - morphine tolerance
OT  - neuropathic pain
EDAT- 2015/11/15 06:00
MHDA- 2016/06/21 06:00
CRDT- 2015/11/15 06:00
PHST- 2015/04/04 00:00 [received]
PHST- 2015/10/12 00:00 [revised]
PHST- 2015/10/20 00:00 [accepted]
PHST- 2015/11/15 06:00 [entrez]
PHST- 2015/11/15 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
AID - 10.1002/ijc.29927 [doi]
PST - ppublish
SO  - Int J Cancer. 2016 Apr 15;138(8):2013-20. doi: 10.1002/ijc.29927. Epub 2015 Dec 
      8.