Chemokine CCL 2 up‐regulated in the medullary dorsal horn astrocytes contributes to nocifensive behaviors induced by experimental tooth movement

To test the hypothesis that the astrocytic chemokine (C‐C motif) ligand 2 ( CCL 2) plays an important role in nocifensive behaviors after experimental tooth movement ( ETM ), the expression and cellular localization of CCL 2 and astrocyte activation in the medullary dorsal horn ( MDH ) were determined by immunohistochemistry in rats. The dose‐dependent effects of intrathecal C‐C chemokine receptor type 2 ( CCR 2) antagonists on these changes in nocifensive behaviors were evaluated. Exogenous CCL 2 was added to medullary dorsal horn slices to evaluate its contributory role in the induction of extracellular signal‐regulated kinase ( ERK ) activation ex vivo. We found a significant increase in the expression of CCL 2 and glial fibrillary acidic protein ( GFAP ), corresponding well to the nocifensive behaviors after ETM . In addition, application of recombinant CCL 2 led to ERK activation, which could be attenuated effectively by pretreatment with CCL 2‐neutralizing antibody ex vivo. The magnitude of the nocifensive behavior could be reduced by medullary CCR 2 antagonists in a dose‐dependent manner. Therefore, the astrocytic CCL 2 is actively involved in the development and maintenance of tooth‐movement pain and thus may be a potential target for analgesics in orthodontic nocifensive responses control.