Pharmacology, Biochemistry and Behavior, Sept, 2014, Vol.124, p.19(8)
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.pbb.2014.05.003 Byline: Yue Liu, Ying Liang, Bailing Hou, Ming Liu, Xuli Yang, Chenglong Liu, Juan Zhang, Wei Zhang, Zhengliang Ma, Xiaoping Gu Abstract: The N-methyl-d-aspartate receptor (NMDAR) containing subunit 2B (NR2B) is critical for the regulation of nociception in bone cancer pain, although the precise molecular mechanisms remain unclear. KIF17, a kinesin motor, plays a key role in the dendritic transport of NR2B. The up-regulation of NR2B and KIF17 transcription results from an increase in phosphorylated cAMP-response element-binding protein (CREB), which is activated by calcium/calmodulin-dependent protein kinase II (CaMKII). In this study, we hypothesized that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. The expression of spinal t-CaMKII, p-CaMKII, NR2B and KIF17 after inoculation was also evaluated. These results showed that inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant up-regulation of p-CaMKII, NR2B and KIF17 expression after inoculation. Intrathecal administration of KN93, a CaMKII inhibitor, down-regulated these three proteins and attenuated bone cancer pain in a dose- and time-dependent manner. These findings indicated that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain, and inhibition of CaMKII may be a useful alternative or adjunct therapy for relieving cancer pain. Article History: Received 11 September 2013; Revised 31 March 2014; Accepted 8 May 2014
Aspartate ; N-Methyl-D-Aspartate ; Cancer Prevention ; Cancer Pain ; Bone Cancer ; Proteins ; Pain Management ; Protein Binding ; Protein Kinases
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