Functional Divergence of Delta and Mu Opioid Receptor Organization in CNS Pain Circuits
| Autor: | Wang, Dong, Tawfik, Vivianne L, Corder, Gregory, Low, Sarah A, François, Amaury, Basbaum, Allan I, Scherrer, Grégory |
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| Přispěvatelé: | Stanford University, 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), University of California [San Francisco] (UCSF), University of California |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Central Nervous System
Male Knockout brain [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Pain neurons Opioid Inbred C57BL Mice delta brainG protein-coupled inwardly rectifying potassium channels Anterior Horn Cells Receptors mental disorders distribution Animals Psychology pain neural circuits mu and delta opioid receptors Pain Measurement Neurology & Neurosurgery Neurosciences spinal cord analgesia co-expression Posterior Horn Cells internalization nervous system mu [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Cognitive Sciences Nerve Net G protein-coupled inwardly rectifying potassium channels |
| Zdroj: | Neuron Neuron, Elsevier, 2018, 98 (1), pp.90-108.e5. ⟨10.1016/j.neuron.2018.03.002⟩ Neuron, vol 98, iss 1 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2018.03.002⟩ |
| Popis: | International audience; Cellular interactions between delta and mu opioid receptors (DORs and MORs), including heteromerization, are thought to regulate opioid analgesia. However, the identity of the nociceptive neurons in which such interactions could occur in vivo remains elusive. Here we show that DOR-MOR co-expression is limited to small populations of excitatory interneurons and projection neurons in the spinal cord dorsal horn and unexpectedly predominates in ventral horn motor circuits. Similarly, DOR-MOR co-expression is rare in parabrachial, amygdalar, and cortical brain regions processing nociceptive information. We further demonstrate that in the discrete DOR-MOR co-expressing nociceptive neurons, the two receptors internalize and function independently. Finally, conditional knockout experiments revealed that DORs selectively regulate mechanical pain by controlling the excitability of somatostatin-positive dorsal horn interneurons. Collectively, our results illuminate the functional organization of DORs and MORs in CNS pain circuits and reappraise the importance of DOR-MOR cellular interactions for developing novel opioid analgesics. |
| Databáze: | OpenAIRE |
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