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

Abstract

Objective: 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. Materials and Methods: 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. Results: 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 magnitudedependent 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. Conclusions: The peripheral CCL2/CCR2 axis is modulated by experimental tooth movement and involved in the development of tooth movement pain. (Angle Orthod. 2014;84:730-736.)

Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat

“…And, exposure to MCP-1 induces an increase in intracellular calcium concentration in 5.8 to 7.9% of acutely dissociated DRG neurons from control rats [14]. Finally, recombinant MCP-1 induces a dose-dependent increase in markers of neuronal activation (Fos) in cultured trigeminal ganglion neurons, which is sensitive to a CCL2 neutralizing antibody [65]. These observations support the suggestion that functional CCR2 is constitutively expressed in sensory neurons.…”

“…While there is no consensus regarding the subpopulation of nociceptors expressing CCR2 [13; 66], it is not expressed by dorsal horn neurons [66]. While, some studies have failed to detect the expression of CCR2 [14; 37; 38; 50], others have provided evidence by means of Western blot [61; 65] and immunofluorescence [8; 13; 66; 68] that CCR2 is constitutively expressed in DRG neurons of naïve rats. Furthermore, in vitro electrophysiological studies performed in DRG neurons obtained from control rats have shown that MCP-1, but not vehicle, activates between 6 to 10% of those neurons [57; 62].…”

Current advances in orthodontic pain

“…Following orthodontic pain, numerous molecules are upregulated in the trigeminal ganglia, for example, P2X3 and CGRP. 61 , 62 , 63 , 64 These molecules change the biological characteristics of trigeminal neurons, for example, increased excitability. 65 With increased excitability, trigeminal neurons are more readily stimulated, resulting in thermal and mechanical hyperalgaesia.…”

Analgesic effects evoked by a CCR2 antagonist or an anti‐CCL2 antibody in inflamed mice

“…Although the relevance of CCR2 in nociceptive processing is well established [6], the demonstration of the presence of these receptors in peripheral nerves remains elusive probably due to a low level of expression, the difficulty to detect them in small structures, or a limited distal transport [7]. Nevertheless, CCR2 mRNA expression has been demonstrated in dorsal root ganglia (DRG) cells of rodents [8], and CCR2 protein has been also detected in rat DRG by both immunohistochemical [7,8] and Western blot [9,10] assays. Although it has been suggested that CCR2 expression could be predominant in smalldiameter DRG cells probably corresponding to nociceptors [7], other authors describe that their presence is similar in medium and large DRG neurons [11].…”