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Minocycline Prevents the Development of Key Features of Inflammation and Pain in DSS-induced Colitis in Mice

  • Author Footnotes
    & Both authors contributed equally to the study
    Teresa Vezza
    Footnotes
    & Both authors contributed equally to the study
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain
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  • Author Footnotes
    & Both authors contributed equally to the study
    Jose Alberto Molina-Tijeras
    Footnotes
    & Both authors contributed equally to the study
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain

    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
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  • Rafael González-Cano
    Correspondence
    Address reprint requests to Rafael González-Cano, Department of Pharmacology, Faculty of Medicine, University of Granada, 18071, Granada, Spain
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain

    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain

    Biomedical Research Center, Institute of Neuroscience, University of Granada, Granada, Spain
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  • Alba Rodríguez-Nogales
    Correspondence
    Address reprint requests to Alba Rodríguez-Nogales, Department of Pharmacology, University of Granada, Avenida del Conocimiento s/n, 18071, Granada, Spain
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain

    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
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  • Federico García
    Affiliations
    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain

    Clinical Microbiology Service, Hospital Universitario San Cecilio, Red de Investigación en SIDA, Granada, Spain
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  • Author Footnotes
    # Both authors contributed equally to the supervision of the study
    Julio Gálvez
    Footnotes
    # Both authors contributed equally to the supervision of the study
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain

    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain

    Centro de Investigación Biomédica en Red – Enfermedades Hepáticas y Digestivas (CIBER-EHD)
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  • Author Footnotes
    # Both authors contributed equally to the supervision of the study
    Enrique J. Cobos
    Footnotes
    # Both authors contributed equally to the supervision of the study
    Affiliations
    Department of Pharmacology, University of Granada, Granada, Spain

    Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain

    Biomedical Research Center, Institute of Neuroscience, University of Granada, Granada, Spain
    Search for articles by this author
  • Author Footnotes
    & Both authors contributed equally to the study
    # Both authors contributed equally to the supervision of the study
Published:September 28, 2022DOI:https://doi.org/10.1016/j.jpain.2022.09.016

      Highlights

      • Minocycline ameliorated inflammation status in experimental colitis
        Minocycline treatment positively impacted gut dysbiosis experimental colitis
        Minocycline decreased referred hyperalgesia and reduced the ongoing pain in DSS model
      • Minocycline might constitute a potential new approach of inflammatory bowel disease (IBD)-induced pain

      Abstract

      Abdominal pain is a common feature in inflammatory bowel disease (IBD) patients, and greatly compromises their quality of life. Therefore, the identification of new therapeutic tools to reduce visceral pain is one of the main goals for IBD therapy. Minocycline, a broad-spectrum tetracycline antibiotic, has gained attention in the scientific community because of its immunomodulatory and anti-inflammatory properties. The aim of this study was to evaluate the potential of this antibiotic as a therapy for the management of visceral pain in dextran sodium sulfate (DSS)-induced colitis in mice. Preemptive treatment with minocycline markedly reduced histological features of intestinal inflammation and the expression of inflammatory markers (Tlr4, Tnfα, Il1ß, Ptgs2, Inos, Cxcl2, and Icam1), and attenuated the decrease of markers of epithelial integrity (Tjp1, Ocln, Muc2, and Muc3). In fact, minocycline restored normal epithelial permeability in colitic mice. Treatment with the antibiotic also reversed the changes in the gut microbiota profile induced by colitis. All these ameliorative effects of minocycline on both inflammation and dysbiosis correlated with a decrease in ongoing pain and referred hyperalgesia, and with the improvement of physical activity induced by the antibiotic in colitic mice. Minocycline might constitute a new therapeutic approach for the treatment of IBD-induced pain.
      Perspective: This study found that the intestinal anti-inflammatory effects of minocycline ameliorate DSS-associated pain in mice. Therefore, minocycline might constitute a novel therapeutic strategy for the treatment of IBD-induced pain.

      Key words

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