PMID- 24886294
OWN - NLM
STAT- MEDLINE
DCOM- 20141017
LR  - 20211021
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 10
DP  - 2014 May 5
TI  - PAR2-mediated upregulation of BDNF contributes to central sensitization in bone 
      cancer pain.
PG  - 28
LID - 10.1186/1744-8069-10-28 [doi]
AB  - BACKGROUND: Bone cancer pain is currently a major clinical challenge for the 
      management of cancer patients, and the cellular and molecular mechanisms 
      underlying the spinal sensitization remain unclear. While several studies 
      demonstrated the critical role of proteinase-activated receptor (PAR2) in the 
      pathogenesis of several types of inflammatory or neuropathic pain, the 
      involvement of spinal PAR2 and the pertinent signaling in the central 
      sensitization is not determined yet in the rodent model of bone cancer pain. 
      FINDINGS: Implantation of tumor cells into the tibias induced significant thermal 
      hyperalgesia and mechanical allodynia, and enhanced glutamatergic strength in the 
      ipsilateral dorsal horn. Significantly increased brain-derived neurotrophic 
      factor (BDNF) expression was detected in the dorsal horn, and blockade of spinal 
      BDNF signaling attenuated the enhancement of glutamatergic strength, thermal 
      hyperalgesia and mechanical allodynia in the rats with bone cancer pain. 
      Significantly increased spinal PAR2 expression was also observed, and inhibition 
      of PAR2 signaling ameliorated BDNF upsurge, enhanced glutamatergic strength, and 
      thermal hyperalgesia and mechanical allodynia. Inhibition of NF-kappaB pathway, the 
      downstream of PAR2 signaling, also significantly decreased the spinal BDNF 
      expression, glutamatergic strength of dorsal horn neurons, and thermal 
      hyperalgesia and mechanical allodynia. CONCLUSION: The present study demonstrated 
      that activation of PAR2 triggered NF-kappaB signaling and significantly upregulated 
      the BDNF function, which critically contributed to the enhancement of 
      glutamatergic transmission in spinal dorsal horn and thermal and mechanical 
      hypersensitivity in the rats with bone cancer. This indicated that PAR2 - NF-kappaB 
      signaling might become a novel target for the treatment of pain in patients with 
      bone cancer.
FAU - Bao, Yanju
AU  - Bao Y
FAU - Hou, Wei
AU  - Hou W
FAU - Liu, Rui
AU  - Liu R
FAU - Gao, Yebo
AU  - Gao Y
FAU - Kong, Xiangying
AU  - Kong X
FAU - Yang, Liping
AU  - Yang L
FAU - Shi, Zhan
AU  - Shi Z
FAU - Li, Weidong
AU  - Li W
FAU - Zheng, Honggang
AU  - Zheng H
FAU - Jiang, Shulong
AU  - Jiang S
FAU - Li, Conghuang
AU  - Li C
FAU - Qin, Yinggang
AU  - Qin Y
FAU - Hua, Baojin
AU  - Hua B
AD  - Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical 
      Sciences, Beixiange 5, Xicheng District, 100053 Beijing, China. 
      huabaojin01@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140505
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuropeptides)
RN  - 0 (Receptor, PAR-2)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Bone Neoplasms/*complications
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carcinoma/*complications
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Agents/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Female
MH  - Hyperalgesia/etiology
MH  - In Vitro Techniques
MH  - NF-kappa B/chemistry/metabolism
MH  - Neoplasms, Experimental
MH  - Neuropeptides/pharmacology
MH  - Pain/*etiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, PAR-2/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Spinal Cord/cytology
MH  - Time Factors
MH  - Up-Regulation/*physiology
PMC - PMC4027994
EDAT- 2014/06/03 06:00
MHDA- 2014/10/18 06:00
PMCR- 2014/05/05
CRDT- 2014/06/03 06:00
PHST- 2013/12/13 00:00 [received]
PHST- 2014/04/28 00:00 [accepted]
PHST- 2014/06/03 06:00 [entrez]
PHST- 2014/06/03 06:00 [pubmed]
PHST- 2014/10/18 06:00 [medline]
PHST- 2014/05/05 00:00 [pmc-release]
AID - 1744-8069-10-28 [pii]
AID - 10.1186/1744-8069-10-28 [doi]
PST - epublish
SO  - Mol Pain. 2014 May 5;10:28. doi: 10.1186/1744-8069-10-28.