title: The critical role of leukotriene B4 in antigen-induced mechanical hyperalgesia in immunised rats.
abstract: 1. We investigated the mediators responsible for mechanical hypersensitivity induced by antigen challenge in rats immunised with ovalbumin (OVA). 2. Challenge with OVA (12.5-100 micro g, intraplantar) caused a dose- and time-dependent mechanical hypersensitivity, which peaked 3 h after, decreased thereafter and reached control levels 24 h later. 3. Levels of TNFalpha, IL-1beta and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were increased in paw skin after antigen challenge. 4. OVA-evoked hypersensitivity was partially inhibited (about 51%) by pretreatment with anti-TNFalpha, IL-1beta and IL-8 sera or with IL-1 receptor antagonist (IL-1ra), but not anti-NGF serum. Pretreatment with thalidomide (45 mg kg(-1)) or pentoxifylline (100 mg kg(-1)) also partially inhibited the hypersensitivity at 1-3 h after challenge. 5. Pretreatment with indomethacin (5 mg kg(-1)) or atenolol (1 mg kg(-1)) reduced the OVA-induced hypersensitivity at 1 and 3 h, but not at 5 h after challenge, while the combination of B(1) and B(2) bradykinin receptor antagonists was ineffective over the same times. 6. Pretreatment with MK886 (5-lipoxygenase-activating protein inhibitor, 3 mg kg(-1)), CP 105696 (LTB(4) receptor antagonist; 3 mg kg(-1)) or dexamethasone (0.5 mg kg(-1)) inhibited the hypersensitivity from 1 to 5 h. Furthermore, LTB(4) levels were increased in the paw skin of challenged rats. 7. In conclusion, our results suggest that the TNFalpha-, IL-1beta- and CINC-1-driven release of prostaglandins, sympathetic amines and LTB(4) mediates the first 3 h of mechanical hypersensitivity induced by antigen challenge in rats. At 5 h after OVA administration, although TNFalpha has some role, LTB(4) is the critical nociceptive mediator.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors.forename: Joice Maria
authors.initials: JM
authors.lastname: Cunha
authors.forename: Daniela
authors.initials: D
authors.lastname: Sachs
authors.forename: Cláudio Azevedo
authors.initials: CA
authors.lastname: Canetti
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Sérgio Henrique
authors.initials: SH
authors.lastname: Ferreira
authors.forename: Fernando Queiroz
authors.initials: FQ
authors.lastname: Cunha
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006930:Hyperalgesia / Q000276:immunology* / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000941:Antigens; D007975:Leukotriene B4; D010047:Ovalbumin