13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: not found

          A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

          A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pain related behaviour in two models of osteoarthritis in the rat knee.

            Osteoarthritis (OA) is a major healthcare burden, with increasing incidence. Pain is the predominant clinical feature, yet therapy is ineffective for many patients. While there are considerable insights into the mechanisms underlying tissue remodelling, there is poor understanding of the link between disease pathology and pain. This is in part owing to the lack of animal models that combine both osteoarthritic tissue remodelling and pain. Here, we provide an analysis of pain related behaviours in two models of OA in the rat: partial medial meniscectomy and iodoacetate injection. Histological studies demonstrated that in both models, progressive osteoarthritic joint pathology developed over the course of the next 28 days. In the ipsilateral hind limb in both models, changes in the percentage bodyweight borne were small, whereas marked mechanical hyperalgesia and tactile allodynia were seen. The responses in the iodoacetate treated animals were generally more robust, and these animals were tested for pharmacological reversal of pain related behaviour. Morphine was able to attenuate hyperalgesia 3, 14 and 28 days after OA induction, and reversed allodynia at days 14 and 28, providing evidence that this behaviour was pain related. Diclofenac and paracetamol were effective 3 days after arthritic induction only, coinciding with a measurable swelling of the knee. Gabapentin varied in its ability to reverse both hyperalgesia and allodynia. The iodoacetate model provides a basis for studies on the mechanisms of pain in OA, and for development of novel therapeutic analgesics.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards.

                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                5 October 2012
                : 7
                : 10
                : e46129
                Affiliations
                [1 ]AstraZeneca R&D Södertälje, CNSP iMed Science, Södertälje, Sweden
                [2 ]AstraZeneca R&D Södertälje, Regulatory Affairs, Södertälje, Sweden
                [3 ]Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
                [4 ]Multidisciplinary Pain Center, Uppsala University Hospital, Uppsala, Sweden
                University of North Dakota, United States of America
                Author notes

                Competing Interests: K. Ängeby Möller, S. Kinert, and O-G. Berge are employed by AstraZeneca R&D Södertälje. At the time of this work, R. Storkson was a consultant at AstraZeneca R&D Södertälje. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: KÄM SK. Performed the experiments: KÄM SK. Analyzed the data: KÄM SK. Contributed reagents/materials/analysis tools: RS. Wrote the paper: KÄM OGB. Designed the software used in analysis: RS.

                Article
                PONE-D-12-11953
                10.1371/journal.pone.0046129
                3465303
                23071540
                03b74ad4-2065-45ad-8752-bad5def0d8a6
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 April 2012
                : 28 August 2012
                Page count
                Pages: 12
                Funding
                This work was funded in full by AstraZeneca R&D Södertälje. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Agriculture
                Animal Management
                Animal Behavior
                Biology
                Immunology
                Immunity
                Inflammation
                Model Organisms
                Animal Models
                Rat
                Neuroscience
                Cognitive Neuroscience
                Pain
                Behavioral Neuroscience
                Neurobiology of Disease and Regeneration
                Medicine
                Clinical Immunology
                Immunity
                Inflammation
                Clinical Research Design
                Preclinical Models
                Drugs and Devices
                Behavioral Pharmacology
                Neurology
                Pain Management
                Rheumatology
                Osteoarthritis
                Rheumatoid Arthritis
                Veterinary Science
                Animal Types
                Laboratory Animals

                Uncategorized
                Uncategorized

                Comments

                Comment on this article