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      Performance of behavioral assays: the Rat Grimace Scale, burrowing activity and a composite behavior score to identify visceral pain in an acute and chronic colitis model

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          Abstract

          Supplemental Digital Content is Available in the Text.

          The ability of spontaneous behavioral assays to assess chronic pain is limited. In colitis, RGS identified acute and chronic pain, burrowing identified acute pain.

          Abstract

          Introduction:

          The Rat Grimace Scale (RGS), a facial expression scale, quantifies the affective component of pain in rats. The RGS was developed to identify acute and inflammatory pain, and applicability in acute and chronic visceral pain is unknown. The dextran sulfate sodium (DSS) colitis model is commonly used in rats, but pain is rarely assessed, instead, disease progression is monitored with the Disease Activity Index (DAI; assessing fecal blood, stool consistency, and weight loss).

          Objectives:

          The aim of this study was to assess whether the RGS and 2 additional behavioral tools (composite behavior score [CBS] and burrowing) could identify pain in an acute and chronic DSS colitis model.

          Methods:

          Male and female Sprague-Dawley rats were block randomized to (1) acute colitis (4 days DSS in drinking water); (2) chronic colitis (4 days DSS, 7 days water, and 3 days DSS); or (3) control (14 days water). Disease Activity Index, RGS, CBS, and burrowing assessments were performed daily.

          Results:

          Rat Grimace Scale scores increased as DAI scores increased during both acute and chronic phases. Burrowing only decreased during the acute phase. By contrast, CBS scores did not increase significantly during either colitis phase.

          Conclusions:

          These data show that the RGS and burrowing did not decrease in a sustained manner during chronic phase visceral pain, and that variables assessed in the DAI are indicative of pain. This suggests that the RGS can be applied to a wider range of pain types and chronicity than originally suggested. These findings increase the application of the RGS as a pain scale and welfare improvement tool.

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          Most cited references27

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          Clinicopathologic study of dextran sulfate sodium experimental murine colitis.

          We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.
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            Pain and inflammatory bowel disease.

            Abdominal pain is a common symptom of inflammatory bowel disease (IBD: Crohn's disease, ulcerative colitis). Pain may arise from different mechanisms, which can include partial blockage and gut distention as well as severe intestinal inflammation. A majority of patients suffering from acute flares of IBD will experience pain, which will typically improve as disease activity decreases. However, a significant percentage of IBD patients continue experiencing symptoms of pain despite resolving inflammation and achieving what appears to be clinical remission. Current evidence suggests that sensory pathways sensitize during inflammation, leading to persistent changes in afferent neurons and central nervous system pain processing. Such persistent pain is not only a simple result of sensory input. Pain processing and even the activation of sensory pathways is modulated by arousal, emotion, and cognitive factors. Considering the high prevalence of iatrogenic as well as essential neuropsychiatric comorbidities including anxiety and depression in IBD patients, these central modulating factors may significantly contribute to the clinical manifestation of chronic pain. The improved understanding of peripheral and central pain mechanisms is leading to new treatment strategies that view pain as a biopsychosocial problem. Thus, improving the underlying inflammation, decreasing the excitability of sensitized afferent pathways, and altering emotional and/or cognitive functions may be required to more effectively address the difficult and disabling disease manifestations.
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              Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards.

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                Author and article information

                Journal
                Pain Rep
                Pain Rep
                PAIREP
                Painreports
                Pain Reports
                Wolters Kluwer (Philadelphia, PA )
                2471-2531
                05 March 2019
                Mar-Apr 2019
                : 4
                : 2
                : e718
                Affiliations
                Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC, Canada
                Author notes
                [* ]Corresponding author. Address: Faculty of Veterinary Medicine, Université de Montréal, 3200 Rue Sicotte, Saint-Hyacinthe, QC J2S 2M2, Canada. E-mail address: daniel.pang@ 123456umontreal.ca (D.S.J. Pang).
                Article
                PAINREPORTS-D-18-0096 00010
                10.1097/PR9.0000000000000712
                6455688
                31041420
                248e3e06-49d0-49a3-89e7-93fbfb84c9f1
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

                This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0 (CC BY-SA) which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 19 October 2018
                : 13 December 2018
                : 16 December 2018
                Categories
                2
                Basic Science
                Research Paper
                Custom metadata
                TRUE
                T

                ongoing pain,pain assessment,animal,rodent,pain behavior,facial expression,spontaneous pain

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