Brain-derived neurotrophic factor modulates N-methyl-D-aspartate receptor activation in a rat model of cancer-induced bone pain
| Autor: | Fu-hai Ji, Jianling Zuo, Xiu-yun Wang, Xiao-hong Jin, Lina Wang, Jianping Yang, Qi-nian Xu, Ying Zhan |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Small interfering RNA
Time Factors Pain Bone Neoplasms Pharmacology Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Cellular and Molecular Neuroscience Neurotrophic factors Ganglia Spinal Medicine Animals RNA Messenger RNA Small Interfering Receptor Brain-derived neurotrophic factor Analysis of Variance business.industry Brain-Derived Neurotrophic Factor Nerve injury Spinal cord Abdominal Pain Rats Gene Expression Regulation Neoplastic Disease Models Animal medicine.anatomical_structure nervous system Spinal Cord Hyperalgesia NMDA receptor Female Microglia medicine.symptom business Neuroscience |
| Zdroj: | Journal of neuroscience research. 90(6) |
| ISSN: | 1097-4547 |
| Popis: | Brain-derived neurotrophic factor (BDNF) released within the spinal cord induces phosphorylation of N-methyl-D-aspartate (NMDA) receptors on the spinal cord neurons. This process is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about the role of BDNF and NMDA receptors in cancer-induced bone pain (CIBP), whose features are unique. This study demonstrates a critical role of the BDNF-modulated NMDA subunit 1 (NR1) in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP, both in the spinal cord and in the dorsal root ganglia (DRG). We selectively suppressed BDNF expression by RNA interference (RNAi) using intrathecal administration of BDNF small interfering RNA (siRNA). Then, we assessed mechanical threshold and spontaneous pain in CIBP rats. Real-time PCR, Western blotting, and fluorescent immunohistochemical staining were used to detect BDNF or NR1 both in vivo and in vitro. BDNF and phospho-NR1 were expressed under CIBP experimental conditions, with expression levels peaking at day 6 (BDNF) or 9 (NR1). Intrathecal BDNF siRNA prevented CIBP at an early stage of tumor growth (days 4-6). However, at later stages (days 10-12), intrathecal BDNF siRNA only attenuated, but did not completely block, the established CIBP. BDNF-induced NMDA receptor activation in the spinal cord or DRG leads to central sensitization and behavioral hypersensitivity. Thus, BDNF might provide a targeting opportunity for alleviating CIBP. |
| Databáze: | OpenAIRE |
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