Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8
Stimulation of μ-opioid receptors (OPRMs) brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully co...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713003495 |
| _version_ | 1819138256593223680 |
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| author | George Shapovalov Dimitra Gkika Maily Devilliers Artem Kondratskyi Dmitri Gordienko Jerome Busserolles Alexandre Bokhobza Alain Eschalier Roman Skryma Natalia Prevarskaya |
| author_facet | George Shapovalov Dimitra Gkika Maily Devilliers Artem Kondratskyi Dmitri Gordienko Jerome Busserolles Alexandre Bokhobza Alain Eschalier Roman Skryma Natalia Prevarskaya |
| author_sort | George Shapovalov |
| collection | DOAJ |
| description | Stimulation of μ-opioid receptors (OPRMs) brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment. |
| first_indexed | 2024-12-22T11:03:53Z |
| format | Article |
| id | doaj.art-8a36bed6f4564b81a08c9c9cfd1dd452 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T11:03:53Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8a36bed6f4564b81a08c9c9cfd1dd4522022-12-21T18:28:23ZengElsevierCell Reports2211-12472013-08-014350451510.1016/j.celrep.2013.07.002Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8George Shapovalov0Dimitra Gkika1Maily Devilliers2Artem Kondratskyi3Dmitri Gordienko4Jerome Busserolles5Alexandre Bokhobza6Alain Eschalier7Roman Skryma8Natalia Prevarskaya9Inserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FrancePharmacologie fondamentale et clinique de la douleur, Clermont Université, Université d’Auvergne, 63001 Clermont-Ferrand, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FrancePharmacologie fondamentale et clinique de la douleur, Clermont Université, Université d’Auvergne, 63001 Clermont-Ferrand, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FrancePharmacologie fondamentale et clinique de la douleur, Clermont Université, Université d’Auvergne, 63001 Clermont-Ferrand, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FranceInserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d’Ascq, FranceStimulation of μ-opioid receptors (OPRMs) brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment.http://www.sciencedirect.com/science/article/pii/S2211124713003495 |
| spellingShingle | George Shapovalov Dimitra Gkika Maily Devilliers Artem Kondratskyi Dmitri Gordienko Jerome Busserolles Alexandre Bokhobza Alain Eschalier Roman Skryma Natalia Prevarskaya Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 Cell Reports |
| title | Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 |
| title_full | Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 |
| title_fullStr | Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 |
| title_full_unstemmed | Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 |
| title_short | Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8 |
| title_sort | opiates modulate thermosensation by internalizing cold receptor trpm8 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713003495 |
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