title: Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice.
abstract: Jararhagin is a hemorrhagic metalloprotease from Bothrops jararaca snake venom. The hyperalgesic mechanisms of jararhagin were investigated focusing on the role of proinflammatory cytokines (TNF-α and IL-1β) and the transcription factor NFκB. Intraplantar administration of jararhagin (1, 10, 100 and 1000 ng/paw) induced mechanical hyperalgesia, and increased TNF-α levels at 1, 3 and 5 h, and IL-1β levels at 0.5, 1 and 3 h after its injection in the paw tissue. Pre-treatment with morphine (2, 6, 12 μg/paw) inhibited jararhagin-induced mechanical hyperagesia. The systemic or local pre-treatment with etanercept (10 mg/kg and 100 μg/paw) and IL-1ra (30 mg/kg and 100 pg/paw) inhibited jararhagin-induced mechanical hyperalgesia. Co-administration of jararhagin (0.1 ng/paw) and TNF-α (0.1 pg/paw) or jararhagin (0.1 ng/paw) and IL-1β (1 pg/paw) enhanced the mechanical hyperalgesia. The systemic or local pre-treatment with PDTC (NFκB inhibitor; 100 mg/kg and 100 μg/paw) inhibited jararhagin-induced mechanical hyperalgesia as well as PDTC decreased the jararhagin-induced production of TNF-α and IL-1β. Thus, these data demonstrate the involvement of pro-inflammatory cytokines TNF-α and IL-1β and nuclear transcription factor NFκB in jararhagin-induced mechanical hyperalgesia indicating that targeting these mechanisms might contribute to reduce the pain induced by B. jararaca snake venom.
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, CEP 86057-970, Cx Postal 10.011, Londrina, Paraná, Brazil. Electronic address: camila_ferraz96@hotmail.com.
authors.forename: Camila R
authors.initials: CR
authors.lastname: Ferraz
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, CEP 86057-970, Cx Postal 10.011, Londrina, Paraná, Brazil. Electronic address: cassia.biom@gmail.com.
authors.forename: Cássia
authors.initials: C
authors.lastname: Calixto-Campos
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, CEP 86057-970, Cx Postal 10.011, Londrina, Paraná, Brazil. Electronic address: marilia_manchope@hotmail.com.
authors.forename: Marília F
authors.initials: MF
authors.lastname: Manchope
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Avenida Robert Koch, 60, CEP 86039-440, Londrina, Paraná, Brazil. Electronic address: rubiacasa@uel.br.
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, Secretaria de Saúde, Av. Vital Brazil, 1500, CEP 05503-900, Butantan, São Paulo, São Paulo, Brazil. Electronic address: clissapb@butantan.gov.br.
authors.forename: Patrícia B
authors.initials: PB
authors.lastname: Clissa
authors.affiliation: Departamento de Bioquímica e Biotecnologia, Centro de Ciências Exatas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, CEP 86057-970, Londrina, Paraná, Brazil. Electronic address: cristianibaldo@yahoo.com.br.
authors.forename: Cristiani
authors.initials: C
authors.lastname: Baldo
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, CEP 86057-970, Cx Postal 10.011, Londrina, Paraná, Brazil. Electronic address: waverri@uel.br.
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006930:Hyperalgesia / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000633:toxicity*; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097146:Bothrops jararaca Venom
chemical_list: D003435:Crotalid Venoms; D005978:Glutathione; D053583:Interleukin-1beta; D008666:Metalloendopeptidases; D009020:Morphine; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000097146:Bothrops jararaca Venom
keywords: Bothrops jararaca; Cytokines; Hyperalgesia; Jararhagin; Metalloprotease; NFκB