title: Cytokine-induced neutrophil chemoattractant 1 (CINC-1) mediates the sympathetic component of inflammatory mechanical hypersensitivitiy in rats.
abstract: The hyperalgesic effect of cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL1) was measured in a model of mechanical hyperalgesia in rats. CINC-1 evoked a dose-dependent mechanical hypersensitivity, which was already significant 2 h after the cytokine injection, peaked 4 h after and decreased thereafter. The local pre-treatment of the rats with the beta-adrenoceptor antagonist, atenolol (25 microg paw-1), but not with the cyclooxygenase inhibitor indomethacin (100 microg paw-1), inhibited (86%) the CINC-1-induced hypersensitivity. Conversely, IL-1beta-evoked hypersensitivity was inhibited (76%) by local pre-treatment of the animals with indomethacin, but not by atenolol. Carrageenin- and TNF-alpha-evoked hypersensitivity were attenuated to about the same extent (50%) by antisera neutralising CINC-1 or IL-1beta. The association of both antisera abolished the hypersensitivity effect of carrageenin and TNF-alpha. In addition, carrageenin, LPS and TNF-alpha were shown to stimulate the production of immunoreactive CINC-1 in the skin of injected paws. These data suggest that CINC-1, released at sites of inflammation, mediates inflammatory hyperalgesia in rats via release of sympathomimetic amines.
authors.affiliation: Department of Pharmacology, Institute of Biological Science, Universidade Federal do Paraná, Brazil.
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Lorenzetti
authors.forename: Fabiane H
authors.initials: FH
authors.lastname: Veiga
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Canetti
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Sérgio H
authors.initials: SH
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D054360:Chemokine CXCL1; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001262:Atenolol; D002351:Carrageenan; D007213:Indomethacin