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Brain-derived neurotrophic factor modulates N-methyl-D-aspartate receptor activation in a rat model of cancer-induced bone pain

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

Keywords : Abdominal Pain,Analysis of Variance,Anesthesiology,Animals,Bone Neoplasms,Brain-Derived Neurotrophic Factor,China,complications,Disease Models,Animal,drug effects,drug therapy,etiology,Female,Ganglia,Spinal,Gene Expression Regulation,Neoplastic,genetics,Growth,Hyperalgesia,injuries,metabolism,Microglia,Neurons,Pain,pathology,Phosphorylation,physiology,Rats,Rats,Sprague-Dawley,Receptors,N-Methyl-D-Aspartate,RNA,Messenger,RNA,Small Interfering,Spinal Cord,therapeutic use,Time Factors,Universities,, Neurotrophic,Factor,Modulates,Nmethyldaspartate,Receptor, colic ureter

Date of Publication : 2012 Jun

Authors : Wang LN;Yang JP;Ji FH;Zhan Y;Jin XH;Xu QN;Wang XY;Zuo JL;

Organisation : Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China

Journal of Publication : J Neurosci Res

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22354476

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Brain-derived neurotrophic factor modulates N-methyl-D-aspartate receptor activation in a rat model of cancer-induced bone pain | Physiotherapy west london

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