Back to Search
Start Over
Chemokine receptor CXCR4 regulates CaMKII/CREB pathway in spinal neurons that underlies cancer-induced bone pain
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI. Intrathecal delivery of CXCR4 siRNA or CaMKII inhibitor AIP2 abrogated TCI-induced pain hypersensitivity and TCI-induced increase in p-CaMKII and p-CREB expression. Intrathecal injection of the principal ligand for CXCR4, SDF-1, promoted p-CaMKII and p-CREB expression in naive rats, which was prevented by post-administration of CXCR4 inhibitor Plerixafor or PLC inhibitor U73122. Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.
- Subjects :
- 0301 basic medicine
Benzylamines
Carcinogenesis
Cyclams
CXCR4
Chemokine receptor
0302 clinical medicine
Heterocyclic Compounds
Estrenes
RNA, Small Interfering
Cyclic AMP Response Element-Binding Protein
Receptor
Injections, Spinal
Neurons
Regulation of gene expression
Membrane Glycoproteins
Multidisciplinary
biology
Cancer Pain
Pyrrolidinones
Gene Expression Regulation, Neoplastic
Spinal Cord
Medicine
medicine.symptom
Neuroglia
Signal Transduction
Receptors, CXCR4
CXCR4 Inhibitor
Science
Bone Neoplasms
CREB
Article
03 medical and health sciences
Ca2+/calmodulin-dependent protein kinase
medicine
Animals
Humans
Bone pain
business.industry
Chemokine CXCL12
Rats
030104 developmental biology
nervous system
Immunology
Cancer research
biology.protein
Calcium-Calmodulin-Dependent Protein Kinase Type 2
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....183fa0d3864ef9387a752b9a16e48da9