期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 124, 期 -, 页码 19-26出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2014.05.003
关键词
Bone cancer pain; N-methyl-D-asparate receptor; N-methyl-D-aspartate receptor 2B subunit; Calcium/calmodulin-dependent protein kinase II; KN93
资金
- National Natural Science Foundation of China [81070892, 81171048, 81171047, 81371207, 81300950, 81300951]
- Jiangsu Natural Science Fund of China [BK2009031]
- Department of Health of Jiangsu Province of China [XK201140, RC2011006]
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 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. (C) 2014 Elsevier Inc. All rights reserved.
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