1. Delta opioid receptors on nociceptive sensory neurons mediate peripheral endogenous analgesia in colitis
- Author
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Xavier Mas-Orea, Lilian Basso, Catherine Blanpied, Claire Gaveriaux-Ruff, Nicolas Cenac, Gilles Dietrich, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INFINITy cellular imaging core facility, ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), SEGUIN, Nathalie, and Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID
- Subjects
Immunology ,T lymphocytes ,Intestinal inflammation ,Cellular and Molecular Neuroscience ,Mice ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Receptors, Opioid, delta ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Intestinal Mucosa ,RC346-429 ,Inflammation ,Mice, Knockout ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,General Neuroscience ,Research ,Nociceptors ,Colitis ,Opioids ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Disease Models, Animal ,Opioid receptors ,Neurology ,Visceral pain ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Neurology. Diseases of the nervous system ,Analgesia ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Inflammatory visceral pain is endogenously controlled by enkephalins locally released by mucosal CD4+ T lymphocytes in mice. The present study aimed at identifying opioid receptor(s) expressed on nociceptive sensory nerves involved in this peripheral opioid-mediated analgesia. Methods The peripheral analgesia associated with the accumulation of CD4+ T lymphocytes within the inflamed colonic mucosa was assessed in conditional knockout mice specifically deleted for either of the two opioid receptors for enkephalins (i.e., µ (MOR) and δ (DOR) receptors) in Nav1.8-expressing sensory neurons in the dextran sulfate sodium (DSS)-induced colitis model. Results Endogenous analgesia is lost in conditional knockout mice for DOR, but not MOR at the later phase of the DSS-induced colitis. The absence of either of the opioid receptors on sensory nerves had no impact on both the colitis severity and the rate of T lymphocytes infiltrating the inflamed colonic mucosa. Conclusion The key role of DOR on primary afferents in relieving intestinal inflammatory pain opens new therapeutic opportunities for peripherally restricted DOR analgesics to avoid most of the side effects associated with MOR-targeting drugs used in intestinal disorders.
- Published
- 2022