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Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord.
Xu, Yang; Liu, Jia; He, Mu; Liu, Ran; Belegu, Visar; Dai, Ping; Liu, Wei; Wang, Wei; Xia, Qing-Jie; Shang, Fei-Fei; Luo, Chao-Zhi; Zhou, Xue; Liu, Su; McDonald, JohnW; Liu, Jin; Zuo, Yun-Xia; Liu, Fei; Wang, Ting-Hua.
Afiliación
  • Xu Y; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Liu J; Institute of Neuroscience, Kunming Medical University, Kunming 650031, PR China.
  • He M; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Liu R; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Belegu V; 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.
  • Dai P; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Liu W; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Wang W; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Xia QJ; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Shang FF; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Luo CZ; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Zhou X; Department of Histology, Embryology and Neurobiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
  • Liu S; 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.
  • McDonald J; 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.
  • Liu J; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Zuo YX; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Liu F; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
  • Wang TH; Institute of Neurological Disease, Department of Anesthesiology and Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Sci Rep ; 6: 27512, 2016 06 10.
Article en En | MEDLINE | ID: mdl-27282805
ABSTRACT
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/ß 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/ß 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.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Médula Espinal / Neoplasias Óseas / Factor de Crecimiento Derivado de Plaquetas / ARN Interferente Pequeño / Dolor en Cáncer Límite: Animals Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Asunto principal: Médula Espinal / Neoplasias Óseas / Factor de Crecimiento Derivado de Plaquetas / ARN Interferente Pequeño / Dolor en Cáncer Límite: Animals Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article