title: 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  The peripheral CCL2/CCR2 axis is modulated by experimental tooth movement and involved in the development of tooth movement pain.
authors.affiliation: a  Research Scientist and Instructor, Department of Oral and Craniomaxillofacial Science, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Tan
authors.forename: Runqing
authors.initials: R
authors.lastname: Fu
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology; D016207:Cytokines / Q000032:analysis* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D013997:Time Factors; D014087:Tooth Movement Techniques / Q000295:instrumentation*; D012668:Trigeminal Ganglion / Q000737:chemistry* / Q000187:drug effects
chemical_list: C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos; D054390:Receptors, CCR2
keywords: CCL2; Experimental tooth movement; Pain; Trigeminal ganglion