title: Using gait analysis to assess weight bearing in rats with Freund׳s complete adjuvant-induced monoarthritis to improve predictivity: Interfering with the cyclooxygenase and nerve growth factor pathways.
abstract: Lack of predictive power for drug effects has been a major criticism against animal pain models. It is therefore important to define the utility and limitations of different models. The aim of this study was to extend previous work on gait analysis as a tool to investigate pharmacological effects in monoarthritic rats, specifically to test the hypothesis that monoarthritis induced by Freund׳s complete adjuvant (FCA) provides a better estimate of overall analgesic efficacy of established, and novel, clinically effective and ineffective therapeutic approaches. Male rats injected intra-articularly into one ankle joint with FCA (1.0mg/ml) were treated with the monoclonal antibody to nerve growth factor (NGF), MEDI-578, the inhibitors of tropomyosin receptor kinases A, B and C (pan-Trk) AZ6623 or AZ7092, the transient receptor potential vanilloid 1 (TRPV1) inhibitor AZD1386, or the cyclooxygenase (COX) inhibitors naproxen, ibuprofen, valdecoxib or rofecoxib. Effects on weight bearing during locomotion were tested using video capture of print images. The apparent efficacy in this model was Trk inhibitors≥anti-NGF antibody>COX inhibitors. The TRPV1 inhibitor was ineffective. Together with previous data, the results support using gait-related parameters in the monoarthritis model. FCA as induction agent seems to provide a good overall prediction of analgesic efficacy in disorders with inflammatory joint pain.
authors: AstraZeneca R&D Södertälje, CNSP iMed Science, SE-151 85 Södertälje, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: kristina.angeby.moller@ki.se.
authors: Kristina
authors: K
authors: Ängeby Möller
authors: AstraZeneca R&D Södertälje, CNSP iMed Science, SE-151 85 Södertälje, Sweden; Multidisciplinary Pain Center, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
authors: Odd-Geir
authors: OG
authors: Berge
authors: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors: Anja
authors: A
authors: Finn
authors: AstraZeneca R&D Södertälje, CNSP iMed Science, SE-151 85 Södertälje, Sweden.
authors: Carina
authors: C
authors: Stenfors
authors: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors: Camilla I
authors: CI
authors: Svensson
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005684:Gait / Q000187:drug effects; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D020932:Nerve Growth Factor; D011451:Prostaglandin-Endoperoxide Synthases; D011494:Protein Kinases; C041311:tropomyosin kinase
keywords: Arthritis; Gait analysis; Nociception; Rat; Weight bearing