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Involvement of spinal chemokine CCL2 in the hyperalgesia evoked by bone cancer in mice: a role for astroglia and microglia.
- Source :
-
Cellular and molecular neurobiology [Cell Mol Neurobiol] 2014 Jan; Vol. 34 (1), pp. 143-56. - Publication Year :
- 2014
-
Abstract
- The hypernociceptive role played by the chemokine CCL2, and its main receptor, CCR2, in pathological settings is being increasingly recognized. We aimed to characterize the involvement of spinal CCL2 in the hyperalgesia due to the intratibial inoculation of fibrosarcoma NCTC 2472 cells in mice. The intrathecal (i.t.) administration of the CCR2 antagonist RS 504393 (1–3 μg) or an anti-CCL2 antibody inhibited tumoral hyperalgesia. No change in the expression of spinal CCR2 was detected by western blot, whereas immunohistochemical experiments demonstrated increased CCL2 staining at the superficial laminae of the spinal cord ipsilateral to the tumor. This spinal CCL2 does not seem to be released from nociceptors since CCL2 mRNA and CCL2 levels in DRGs, as measured by RT-PCR and ELISA, remain unmodified in tumor-bearing mice. In contrast, immunohistochemical assays demonstrated the spinal up-regulations of GFAP and Iba-1, respective markers of astroglia and microglia, and the expression of CCL2 in both types of glial cells at the superficial laminae of the spinal cord of tumor-bearing mice. Finally, since CCL2 could induce astroglial or microglial activation, we studied whether the blockade of CCR2 could inhibit the increased spinal glial expression. GFAP, but not Iba-1, up-regulation was reduced in tumor-bearing mice treated for 3 days with i.t. RS 504393, indicating that spinal CCL2 acts as an astroglial activator in this setting. The participation at spinal level of CCL2/CCR2 in tumoral hypernociception, together with its previously described involvement at periphery, makes attractive the modulation of this system for the alleviation of neoplastic pain.
- Subjects :
- Animals
Astrocytes drug effects
Benzoxazines pharmacology
Blotting, Western
Cell Line, Tumor
Chemokine CCL2 genetics
Enzyme-Linked Immunosorbent Assay
Ganglia, Spinal pathology
Glial Fibrillary Acidic Protein metabolism
Immunohistochemistry
Lumbar Vertebrae drug effects
Lumbar Vertebrae metabolism
Lumbar Vertebrae pathology
Mice
Microglia drug effects
Neurons drug effects
Neurons metabolism
Neurons pathology
Protein Transport drug effects
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, CCR2 antagonists & inhibitors
Receptors, CCR2 metabolism
Spinal Cord drug effects
Spinal Cord pathology
Spiro Compounds pharmacology
Up-Regulation drug effects
Astrocytes metabolism
Bone Neoplasms complications
Chemokine CCL2 metabolism
Hyperalgesia etiology
Microglia metabolism
Osteosarcoma complications
Spinal Cord metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6830
- Volume :
- 34
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular and molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 24122510
- Full Text :
- https://doi.org/10.1007/s10571-013-9995-7