Chemokine ligand 2 in the trigeminal ganglion regulates pain induced by experimental tooth movement

Abstract

To test the hypothesis that the chemokine ligand 2/chemokine receptor 2 (CCL2/CCR2) signaling pathway plays an important role in pain induced by experimental tooth movement. Expression of CCL2/CCR2 in the trigeminal ganglion (TG) was determined by Western blotting 0 hours, 4 hours, 1 day, 3 days, 5 days, and 7 days after tooth movement. CCL2 localization and cell size distribution were revealed by immunohistochemistry. The effects of increasing force on CCL2 expression and behavioral changes were investigated. Furthermore, the effects of CCL2/CCR2 antagonists on these changes in pain behaviors were all evaluated. Exogenous CCL2 was injected into periodontal tissues and cultured TG neurons with different concentrations, and then the pain responses or c-fos expression were assessed. Experimental tooth movement led to a statistically significant increase in CCL2/CCR2 expression from day 3 to day 7, especially in small to medium-sized TG neurons. It also triggered an increase in the time spent on directed face-grooming behaviors in a force magnitude-dependent and CCL2 dose-dependent manner. Pain induced by experimental tooth movement was effectively blocked by a CCR2 antagonist and by CCL2 neutralizing antibody. Also, exogenous CCL2 led to an increase in c-fos expression in cultured TG neurons, which was blocked by CCL2 neutralizing antibody. The peripheral CCL2/CCR2 axis is modulated by experimental tooth movement and involved in the development of tooth movement pain.