title: CCL2 released at tumoral level contributes to the hyperalgesia evoked by intratibial inoculation of NCTC 2472 but not B16-F10 cells in mice.
abstract: The participation of the chemokine CCL2 (monocyte chemoattractant protein-1) in inflammatory and neuropathic pain is well established. Furthermore, the release of CCL2 from a NCTC 2472 cells-evoked tumor and its involvement in the upregulation of calcium channel α2δ1 subunit of nociceptors was demonstrated. In the present experiments, we have tried to determine whether the increase in CCL2 levels is a common property of painful tumors and, in consequence, the administration of a chemokine receptor type 2 (CCR2) antagonist can inhibit tumoral hypernociception. CCL2 levels were measured by ELISA in the tumoral region of mice intratibially inoculated with NCTC 2472 or B16-F10 cells, and the antihyperalgesic and antiallodynic effects evoked by the administration of the selective CCR2 antagonist RS 504393 were assessed. Cultured NCTC 2472 cells release CCL2 and their intratibial inoculation evokes the development of a tumor in which CCL2 levels are increased. Moreover, the systemic or peritumoral administration of RS 504393 inhibited thermal and mechanical hyperalgesia, but not mechanical allodynia evoked after the inoculation of these cells. Thermal hyperalgesia was also inhibited by the peritumoral administration of a neutralizing CCL2 antibody. In contrast, no change in CCL2 levels was observed in mice inoculated with B16-F10 cells, and RS 504393 did not inhibit the hypernociceptive reactions evoked by their intratibial inoculation. The peripheral release of CCL2 is involved in the development of thermal and mechanical hyperalgesia, but not mechanical allodynia evoked by the inoculation of NCTC 2472 cells, whereas this chemokine seems unrelated to the hypernociception induced by B16-F10 cells.
authors.affiliation: Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, c/ Julián Clavería 6, 33006, Oviedo, Asturias, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pevida
authors.forename: Sara
authors.initials: S
authors.lastname: González-Rodríguez
authors.forename: Ana
authors.initials: A
authors.lastname: Lastra
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez
authors.forename: Ana
authors.initials: A
authors.lastname: Baamonde
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000150:complications* / Q000556:secondary; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013977:Tibia
chemical_list: D048588:Benzoxazines; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; C579117:RS 504393; D054390:Receptors, CCR2; D013141:Spiro Compounds