TRPV1 promotes opioid analgesia during inflammation
| العنوان: | TRPV1 promotes opioid analgesia during inflammation |
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| المؤلفون: | Christophe Altier, Emmanuel Bourinet, Tuan Trang, Helvira Melo, Francina Agosti, Robyn Flynn, Roger J. Thompson, Morley D. Hollenberg, Mircea Iftinca, Lilian Basso, Reem Aboushousha, Churmy Y. Fan |
| المساهمون: | Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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 de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Departments of Physiology & Pharmacology, and Medicine [Calgary, Canada] (School of Medicine), University of Calgary, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT) |
| المصدر: | Science Signaling Science Signaling, American Association for the Advancement of Science, 2019, 12 Science Signaling, American Association for the Advancement of Science, 2019, 12, ⟨10.1126/scisignal.aav0711⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | medicine.drug_class, Narcotic Antagonists, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Freund's Adjuvant, Analgesic, TRPV1, TRPV Cation Channels, Pharmacology, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Desensitization (telecommunications), Opioid receptor, medicine, Animals, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Endogenous opioid, Inflammation, Mice, Knockout, 0303 health sciences, Naloxone, business.industry, Chronic pain, Cell Biology, medicine.disease, Acute Pain, beta-Arrestin 2, Analgesics, Opioid, Quaternary Ammonium Compounds, Disease Models, Animal, nervous system, Opioid, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Analgesia, Chronic Pain, Signal transduction, business, 030217 neurology & neurosurgery, Signal Transduction, medicine.drug |
| الوصف: | Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute inflammation in humans or mice enhances the analgesic properties of opioids, there is much interest in determining the inflammatory transducers that prime opioid receptor signaling in primary afferent nociceptors. Here, we found that activation of the transient receptor potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) signaling pathway that was accompanied by the shuttling of the scaffold protein β-arrestin2 to the nucleus. The nuclear translocation of β-arrestin2 in turn prevented its recruitment to the μ-opioid receptor (MOR), the subsequent internalization of agonist-bound MOR, and the suppression of MOR activity that occurs upon receptor desensitization. Using the complete Freund's adjuvant (CFA) inflammatory pain model to examine the role of TRPV1 in regulating endogenous opioid analgesia in mice, we found that naloxone methiodide (Nal-M), a peripherally restricted, nonselective, and competitive opioid receptor antagonist, slowed the recovery from CFA-induced hypersensitivity in wild-type, but not TRPV1-deficient, mice. Furthermore, we showed that inflammation prolonged morphine-induced antinociception in a mouse model of opioid receptor desensitization, a process that depended on TRPV1. Together, our data reveal a TRPV1-mediated signaling pathway that serves as an endogenous pain-resolution mechanism by promoting the nuclear translocation of β-arrestin2 to minimize MOR desensitization. This previously uncharacterized mechanism may underlie the peripheral opioid control of inflammatory pain. Dysregulation of the TRPV1-β-arrestin2 axis may thus contribute to the transition from acute to chronic pain. |
| اللغة: | English |
| تدمد: | 1937-9145 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b61006153d40e2ec71410fc3355d694 https://hal.archives-ouvertes.fr/hal-02356255 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3b61006153d40e2ec71410fc3355d694 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19379145 |
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