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      Advanced Dynamic Weight Bearing as an Observer-independent Measure of Hyperacute Hypersensitivity in Mice

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          ABSTRACT

          Background

          Standard methods assessing pain in rodents are often observer dependent, potentially resulting in biased outcomes. Advanced dynamic weight bearing (ADWB) offers an observer-independent approach that can provide objective, reliable data in preclinical pain research.

          Aims

          The aim of this study was to characterize the use of ADWB in assessing murine responses to allyl isothiocyanate (AITC)-induced hyperacute hypersensitivity and identify best practices for use of the device.

          Methods

          Male C57BL/6J mice received intraplantar injections of saline or 0.1% AITC solution and were assessed using the ADWB system; simultaneous observer-dependent durations of paw licking and biting were measured. ADWB data were analyzed using the proprietary software from Bioseb and correlated to observer-dependent results, with parameters assessed to optimize data collected.

          Results

          ADWB detected pain-directed changes in weight and surface area distribution in AITC-treated mice, with paw weight and surface area placement correlating to paw licking and biting. Optimization of adjustable threshold parameters allowed for reduced coefficients of variability and increased duration of validated data.

          Conclusions

          The ADWB assay provides an efficient and unbiased measure of chemical-induced hyperacute hypersensitivity in mice. ADWB detection parameters influence amount of validated data and variability, a consideration for data analysis in future studies.

          RÉSUMÉ

          Contexte: Les méthodes standard d’évaluation de la douleur chez les rongeurs dépendent souvent de l’observateur, ce qui peut fausser les résultats. La mise en charge dynamique avancée offre une approche indépendante de l’observateur qui peut fournir des données objectives et fiables dans la recherche préclinique sur la douleur.

          Objectifs: L’objectif de cette étude était de caractériser l’utilisation de la mise en charge dynamique avancée dans l’évaluation des réponses murines à l’hypersensibilité hyperaiguë induite par l’isothiocyanate d’allyle et de répertorier les meilleures pratiques d’utilisation de l’appareil.

          Méthodes: Des souris C57BL/6J mâles ont reçu des injections intraplantaires de solution saline ou de solution d’isothiocyanate d’allyle à 0,1 % et ont été évaluées à l’aide du système de mise en charge dynamique avancée; les durées simultanées de léchage et de morsure des pattes, dépendantes de l’observateur, ont été mesurées. Les données obtenues par la mise en charge dynamique avancée ont été analysées à l’aide du logiciel propriétaire de Bioseb et corrélées aux résultats dépendants de l’observateur, avec des paramètres évalués pour optimiser les données collectées.

          Résultats: L’essai réalisé à l’aide de la mise en charge dynamique avancée a détecté des changements de poids et de distribution de surface liés à la douleur chez les souris traitées à l’isothiocyanate d’allyle, le poids des pattes et le placement de la surface étant corrélés au léchage et à la morsure des pattes. L’optimisation des paramètres de seuil ajustables a permis de réduire les coefficients de variabilité et d’augmenter la durée des données validées.

          Conclusion: L’essai réalisé à l’aide de la mise en charge dynamique avancée fournit une mesure efficace et impartiale de l’hypersensibilité hyperaiguë induite par les produits chimiques chez la souris. Les paramètres de détection du système de mise en charge dynamique avancée influencent la quantité de données validées et la variabilité, ce qui doit être pris en compte pour l’analyse des données dans les études futures.

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          Most cited references70

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          DeepLabCut: markerless pose estimation of user-defined body parts with deep learning

          Quantifying behavior is crucial for many applications in neuroscience. Videography provides easy methods for the observation and recording of animal behavior in diverse settings, yet extracting particular aspects of a behavior for further analysis can be highly time consuming. In motor control studies, humans or other animals are often marked with reflective markers to assist with computer-based tracking, but markers are intrusive, and the number and location of the markers must be determined a priori. Here we present an efficient method for markerless pose estimation based on transfer learning with deep neural networks that achieves excellent results with minimal training data. We demonstrate the versatility of this framework by tracking various body parts in multiple species across a broad collection of behaviors. Remarkably, even when only a small number of frames are labeled (~200), the algorithm achieves excellent tracking performance on test frames that is comparable to human accuracy.
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            Cellular and molecular mechanisms of pain.

            The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
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              A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man

              A peripheral mononeuropathy was produced in adult rats by placing loosely constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and, possibly, spontaneous pain (or dysesthesia) were produced. Hyperalgesic responses to noxious radiant heat were evident on the second postoperative day and lasted for over 2 months. Hyperalgesic responses to chemogenic pain were also present. The presence of allodynia was inferred from the nocifensive responses evoked by standing on an innocuous, chilled metal floor or by innocuous mechanical stimulation, and by the rats' persistence in holding the hind paw in a guarded position. The presence of spontaneous pain was suggested by a suppression of appetite and by the frequent occurrence of apparently spontaneous nocifensive responses. The affected hind paw was abnormally warm or cool in about one-third of the rats. About one-half of the rats developed grossly overgrown claws on the affected side. Experiments with this animal model may advance our understanding of the neural mechanisms of neuropathic pain disorders in humans.
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                Author and article information

                Journal
                Can J Pain
                Can J Pain
                Canadian Journal of Pain
                Taylor & Francis
                2474-0527
                21 August 2023
                2023
                21 August 2023
                : 7
                : 2 , Future of Canadian Pain Research: Highlighting Trainee Contributions
                : 2249060
                Affiliations
                [a ] Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada;
                [b ] Department of Anesthesiology & Perioperative Medicine, Kingston Health Sciences Centre, Kingston, Ontario, Canada;
                [c ] Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada;
                Author notes
                CONTACT Nader Ghasemlou nader.ghasemlou@ 123456queensu.ca Botterell Hall, Queen’s University; , 18 Stuart St. Room 754 Kingston, ON K7L 3N6, Canada.
                Author information
                https://orcid.org/0000-0002-0990-0107
                https://orcid.org/0000-0003-4127-4262
                https://orcid.org/0000-0002-6316-1624
                https://orcid.org/0000-0003-3491-4065
                https://orcid.org/0000-0003-0118-0210
                https://orcid.org/0000-0003-0365-5953
                https://orcid.org/0000-0001-8961-3572
                https://orcid.org/0000-0002-1696-7342
                Article
                2249060
                10.1080/24740527.2023.2249060
                10599184
                37885834
                eb986c5f-544d-4eba-a53e-6641623dbda8
                © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

                History
                Page count
                Figures: 6, References: 70, Pages: 1
                Categories
                Research Article
                Research Article

                advanced dynamic weight bearing (adwb),chemical pain,mechanical hypersensitivity,observer-dependent tests,trpa1,allyl isothyocianate (aitc)

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