机构：[1]Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, WestChina Hospital, Sichuan University, Chengdu 610041, PR China[2]Institute of Neuroscience, Kunming MedicalUniversity, Kunming 650031, PR China[3]Department of Neurosurgery, West China Hospital, Sichuan University,Chengdu 610041, PR China四川大学华西医院[4]Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA,International Center for Spinal Cord Injury, Hugo W.Moser Research Institute at Kennedy Krieger Inc.,Baltimore,MD, USA[5]Department of Histology, Embryology and Neurobiology, West China School of Preclinical and ForensicMedicine, Sichuan University, Chengdu, Sichuan 610041, China
Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/β and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/β levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway.
基金：
National Natural Science Foundation of China (Grant No. 81271358
and No. 81171176). It also supported by Specialized Research Fund for the Doctoral Program of Higher Education
(SRFDP) of China (Grant No. 20130181110077).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
最新[2023]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
第一作者：
第一作者机构：[1]Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, WestChina Hospital, Sichuan University, Chengdu 610041, PR China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, WestChina Hospital, Sichuan University, Chengdu 610041, PR China[2]Institute of Neuroscience, Kunming MedicalUniversity, Kunming 650031, PR China
推荐引用方式(GB/T 7714)：
Xu Yang,Liu Jia,He Mu,et al.Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord.[J].Scientific reports.2016,6:27512.doi:10.1038/srep27512.
APA：
Xu Yang,Liu Jia,He Mu,Liu Ran,Belegu Visar...&Wang Ting-Hua.(2016).Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord..Scientific reports,6,
MLA：
Xu Yang,et al."Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord.".Scientific reports 6.(2016):27512
