Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice

Abstract Cardiotoxin injection is a commonly used method to induce muscle damage for studying skeletal muscle regeneration. Toxic injuries cause extensive myofiber damage and necrosis, leading to widespread muscle injury. This model results in an important macrophage infiltration, the release of che...

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Main Authors: Charline Jomard, Natacha Boyer, Aurélie Fessard, Bénédicte Chazaud, Julien Gondin
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13118-9
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author Charline Jomard
Natacha Boyer
Aurélie Fessard
Bénédicte Chazaud
Julien Gondin
author_facet Charline Jomard
Natacha Boyer
Aurélie Fessard
Bénédicte Chazaud
Julien Gondin
author_sort Charline Jomard
collection DOAJ
description Abstract Cardiotoxin injection is a commonly used method to induce muscle damage for studying skeletal muscle regeneration. Toxic injuries cause extensive myofiber damage and necrosis, leading to widespread muscle injury. This model results in an important macrophage infiltration, the release of chemical mediators and the activation of nociceptors, which may result in muscle pain. Managing pain in animal research is critical from both an ethical and scientific perspectives. The goal of this study was to evaluate whether two widely used analgesics, paracetamol and buprenorphine, affect mouse locomotor activity, mechanical sensitivity and muscle regeneration following cardiotoxin injection. Pain was assessed through the Von Frey test and voluntary wheel-running activity recordings. In parallel, we quantified histological and cellular markers of muscle regeneration and assessed the inflammatory response using flow cytometry. Although buprenorphine alleviated stimulus-evoked pain behaviors, none of the analgesics minimized cardiotoxin-induced reduction in wheel-running activity nor affected muscle regeneration and the inflammatory response following injury. Both paracetamol and buprenorphine may even negatively impact spontaneous activity. These findings demonstrate that cardiotoxin-induced muscle injury markedly impairs spontaneous locomotor activity, an effect that may be further amplified by the administration of analgesics. Our findings raise questions about the effectiveness of these pharmacological approaches in pain management after muscle injury, particularly when administrated within the first 24 h post-injury.
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spelling doaj-art-e9b5729ee10e4d93870a94c8c4c8f8092025-08-20T03:45:59ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-13118-9Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in miceCharline Jomard0Natacha Boyer1Aurélie Fessard2Bénédicte Chazaud3Julien Gondin4Institut NeuroMyoGène (INMG), Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315Institut NeuroMyoGène (INMG), Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315Institut NeuroMyoGène (INMG), Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315Institut NeuroMyoGène (INMG), Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315Institut NeuroMyoGène (INMG), Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315Abstract Cardiotoxin injection is a commonly used method to induce muscle damage for studying skeletal muscle regeneration. Toxic injuries cause extensive myofiber damage and necrosis, leading to widespread muscle injury. This model results in an important macrophage infiltration, the release of chemical mediators and the activation of nociceptors, which may result in muscle pain. Managing pain in animal research is critical from both an ethical and scientific perspectives. The goal of this study was to evaluate whether two widely used analgesics, paracetamol and buprenorphine, affect mouse locomotor activity, mechanical sensitivity and muscle regeneration following cardiotoxin injection. Pain was assessed through the Von Frey test and voluntary wheel-running activity recordings. In parallel, we quantified histological and cellular markers of muscle regeneration and assessed the inflammatory response using flow cytometry. Although buprenorphine alleviated stimulus-evoked pain behaviors, none of the analgesics minimized cardiotoxin-induced reduction in wheel-running activity nor affected muscle regeneration and the inflammatory response following injury. Both paracetamol and buprenorphine may even negatively impact spontaneous activity. These findings demonstrate that cardiotoxin-induced muscle injury markedly impairs spontaneous locomotor activity, an effect that may be further amplified by the administration of analgesics. Our findings raise questions about the effectiveness of these pharmacological approaches in pain management after muscle injury, particularly when administrated within the first 24 h post-injury.https://doi.org/10.1038/s41598-025-13118-9AnalgesicsMuscleRegenerationWheel running
spellingShingle Charline Jomard
Natacha Boyer
Aurélie Fessard
Bénédicte Chazaud
Julien Gondin
Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
Scientific Reports
Analgesics
Muscle
Regeneration
Wheel running
title Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
title_full Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
title_fullStr Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
title_full_unstemmed Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
title_short Effect of analgesic treatments on voluntary activity, mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
title_sort effect of analgesic treatments on voluntary activity mechanical sensitivity and muscle regeneration after cardiotoxin injection in mice
topic Analgesics
Muscle
Regeneration
Wheel running
url https://doi.org/10.1038/s41598-025-13118-9
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