title: Hypernociception elicited by tibio-tarsal joint flexion in mice: a novel experimental arthritis model for pharmacological screening.
abstract: Mice have been used as animal model to study mechanisms underlying inflammatory and immune diseases. The present study describes a model of joint inflammation-induced hypernociception to discriminate pharmacological tests in mice. A polypropylene tip probe with a large area (4.15 mm2) applied on the plantar surface of the hind paw was used to produce a dorsal flexion of tibio-tarsal joint. Experiments were performed to demonstrate that the probe application did not provoke cutaneous nociception. The decrease in the withdrawal threshold of inflamed joint was used as nociceptive parameter. Administration of zymosan in the tibio-tarsal joint induced a dose and time-dependent hypernociception elicited by articular dorsal flexion movement. Maximal joint hypernociception was detected between 7 and 24 h after zymosan injection, and matched maximal inflammation score as determined by histopathology and neutrophil migration assay. In agreement with the inflammatory hypernociceptive paradigm, flexion-elicited hypernociception induced by zymosan was dose-dependently inhibited by morphine (2-8 mg/kg) and by an effective dose of indomethacin (5 mg/kg). The present study demonstrated that the tibio-tarsal flexion reflex is a behavioral nociceptive model that allows a quantitative evaluation of inflammatory joint hypernociception in mice and its pharmacological modulation.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, São Paulo, Avenida Bandeirantes, 3900, 14049-900 - Ribeirao Preto, São Paulo, Brazil.
authors.forename: Ana T G
authors.initials: AT
authors.lastname: Guerrero
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.forename: Tarcilia A
authors.initials: TA
authors.lastname: Silva
authors.forename: Francisco A C
authors.initials: FA
authors.lastname: Rocha
authors.forename: Sérgio H
authors.initials: SH
authors.lastname: Ferreira
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Parada
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006614:Hindlimb; D007213:Indomethacin / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D010147:Pain Measurement / Q000295:instrumentation / Q000379:methods*; D011312:Pressure; D013640:Tarsal Joints / Q000187:drug effects / Q000473:pathology; D015054:Zymosan
chemical_list: D016861:Cyclooxygenase Inhibitors; D009020:Morphine; D015054:Zymosan; D008012:Lidocaine; D007213:Indomethacin