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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
CNSP iMed Sci, AstraZeneca R&D Sodertalje, SE-15185 Sodertalje, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden..
CNSP iMed Sci, AstraZeneca R&D Sodertalje, SE-15185 Sodertalje, Sweden.;Univ Uppsala Hosp, Multidisciplinary Pain Ctr, SE-75185 Uppsala, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden..
CNSP iMed Sci, AstraZeneca R&D Sodertalje, SE-15185 Sodertalje, Sweden..
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2015 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 756, 75-84 p.Article in journal (Refereed) Published
Abstract [en]

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. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
2015. Vol. 756, 75-84 p.
Keyword [en]
Arthritis, Rat, Gait analysis, Weight bearing, Nociception
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-304595DOI: 10.1016/j.ejphar.2015.02.050ISI: 000353195600011OAI: oai:DiVA.org:uu-304595DiVA: diva2:1033334
Available from: 2016-10-06 Created: 2016-10-06 Last updated: 2017-11-30Bibliographically approved

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