title: Chemokine CCL2 up-regulated in the medullary dorsal horn astrocytes contributes to nocifensive behaviors induced by experimental tooth movement.
abstract: To test the hypothesis that the astrocytic chemokine (C-C motif) ligand 2 (CCL2) plays an important role in nocifensive behaviors after experimental tooth movement (ETM), the expression and cellular localization of CCL2 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 (CCR2) antagonists on these changes in nocifensive behaviors were evaluated. Exogenous CCL2 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 CCL2 and glial fibrillary acidic protein (GFAP), corresponding well to the nocifensive behaviors after ETM. In addition, application of recombinant CCL2 led to ERK activation, which could be attenuated effectively by pretreatment with CCL2-neutralizing antibody ex vivo. The magnitude of the nocifensive behavior could be reduced by medullary CCR2 antagonists in a dose-dependent manner. Therefore, the astrocytic CCL2 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.
authors.affiliation: Department of Orthodontics, Shanghai Stomatological Disease Center, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Runqing
authors.initials: R
authors.lastname: Fu
authors.forename: Yu
authors.initials: Y
authors.lastname: Tan
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000517:prevention & control; D007091:Image Processing, Computer-Assisted / Q000379:methods; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors; D014087:Tooth Movement Techniques / Q000009:adverse effects*; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000700:Analgesics; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D054390:Receptors, CCR2
keywords: astrocyte; chemokine (C-C motif) ligand 2 (CCL2); experimental tooth movement; medullary dorsal horn; nocifensive behavior