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Brain‐derived neurotrophic factor modulates N‐methyl‐ D ‐aspartate receptor activation in a rat model of cancer‐induced bone pain
Author(s) -
Wang LiNa,
Yang JianPing,
Ji Fuhai,
Zhan Ying,
Jin Xiaohong,
Xu QiNian,
Wang XiuYun,
Zuo JianLing
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22815
Subject(s) - brain derived neurotrophic factor , neurotrophic factors , nmda receptor , spinal cord , medicine , small interfering rna , neuropathic pain , glutamate receptor , tropomyosin receptor kinase b , pharmacology , receptor , endocrinology , chemistry , anesthesia , neuroscience , biology , rna , biochemistry , gene
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. © 2012 Wiley Priodicals, Inc.