title: Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice.
abstract: Chemokines are chemotactic cytokines whose involvement in nociceptive processing is being increasingly recognized. Based on the previous description of the involvement of CC chemokine receptor type 1 (CCR1) in pathological pain, we have assessed the participation of CCR1 and its endogenous ligands CCL3 and CCL5 in hyperalgesia and allodynia in mice after acute inflammation with carrageenan and chronic inflammation with complete Freund's adjuvant (CFA). The subcutaneous administration of the CCR1 antagonist J113863 (3-30 mg/kg; 30 min. before) dose dependently inhibited carrageenan- and CFA-evoked thermal hyperalgesia and mechanical allodynia produced by CFA, but not by carrageenan. The maximal dose of J113863 did not modify the increase in paw thickness induced by carrageenan or CFA. An almost ten times augmentation of CCL3 levels was detected by ELISA assays in both carrageenan and CFA paws, but not in spinal cords of inflamed mice, whereas CCL5 concentrations remained unaltered. Accordingly, a marked increase of CCL3 mRNA expression was observed in inflamed paws, with CCL3 protein detected in neutrophils and macrophages by immunohistochemical experiments. The intraplantar administration of an anti-CCL3 antibody (0.3-3 μg) blocked thermal hyperalgesia in carrageenan- and CFA-inflamed mice as well as CFA-evoked mechanical allodynia. Our data suggest that the increased concentrations of CCL3 present in inflamed tissues can be involved in acute and chronic inflammatory hyperalgesia as well as in chronic mechanical allodynia, and that these hypernociceptive symptoms can be counteracted by its neutralization with an antibody or by the blockade of CCR1 receptors.
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Llorián-Salvador
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: González-Rodríguez
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lastra
authors.affiliation: Molecular Histopathology in Animal Models of Cancer Unit, IUOPA, University of Oviedo, Asturias, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Fernández-García
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez
authors.affiliation: Laboratory of Pharmacology, School of Medicine, University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Baamonde
mesh_terms: D059787:Acute Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D059350:Chronic Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D012333:RNA, Messenger; D054389:Receptors, CCR1; D014966:Xanthenes; D002351:Carrageenan; D005620:Freund's Adjuvant; C413447:UCB 35625