Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord
| Autor: | Jia Liu, Ping Dai, Johnw McDonald, Su Liu, Yun Xia Zuo, Wei Liu, Jin Liu, Visar Belegu, Yang Xu, Mu He, Chao Zhi Luo, Xue Zhou, Fei Liu, Ting Hua Wang, Wei Wang, Ran Liu, Qing Jie Xia, Fei Fei Shang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Small interfering RNA medicine.medical_treatment Down-Regulation Bone Neoplasms Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine medicine Animals Simplexvirus Receptors Platelet-Derived Growth Factor RNA Small Interfering Protein kinase B Platelet-Derived Growth Factor Multidisciplinary Morphine Tibia biology business.industry Bone cancer Growth factor Cancer Pain medicine.disease Rats 030104 developmental biology medicine.anatomical_structure Spinal Cord Hyperalgesia Astrocytes Anesthesia Cancer research biology.protein Female medicine.symptom business 030217 neurology & neurosurgery Platelet-derived growth factor receptor Signal Transduction Astrocyte |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep27512 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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