Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator
| Autor: | Marc López-Cano, Jean-Philippe Pin, Paola Di Pietro, Giuseppe Battaglia, Francisco Ciruela, Pamela Scarselli, Xavier Rovira, Joan Font, Amadeu Llebaria, Cyril Goudet, Jesús Giraldo, Serena Notartomaso, Víctor Fernández-Dueñas, Roger Bresolí-Obach, Juan Lorenzo Catena, Ferdinando Nicoletti, Fanny Malhaire, Santi Nonell |
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| Přispěvatelé: | Universitat Ramon Llull. IQS, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Institute for Advanced Chemistry of Catalonia, Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Universitat Ramon Llull [Barcelona] (URL), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Instituto de Salud Carlos III [Madrid] (ISC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Goudet, Cyril, Universitat de Barcelona |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Life Sciences & Biomedicine - Other Topics Pharmacology neuroscience 0302 clinical medicine Light-operated drugs Malalties cròniques Neurociències Pain treatment Biology (General) BRAIN Receptor allosteric modulation Chemistry METABOTROPIC GLUTAMATE RECEPTORS General Neuroscience genetics and molecular biology (all) Glutamate receptor Chronic pain DORSAL-HORN NEURONS analgesia General Medicine Raseglurant 3. Good health ANIMAL-MODELS Medicine [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] mGlu5 Complex diseases Life Sciences & Biomedicine Farmacologia Allosteric modulator DIFFERENTIAL ROLES QH301-705.5 Ratolins (Animals de laboratori) Science Allosteric regulation Optical control MGLUR5 General Biochemistry Genetics and Molecular Biology MECHANISMS 03 medical and health sciences Tractament del dolor In vivo TARGETS medicine biochemistry [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Analgèsia medicine (all) Biology mouse Science & Technology General Immunology and Microbiology receptor negative allosteric modulator 615 - Farmacologia. Terapèutica. Toxicologia. Radiologia Neurosciences pain neuraxis medicine.disease optopharmacology mGlu5 receptor neuroscience (all) immunology and microbiology (all) biochemistry genetics and molecular biology (all) MICE 030104 developmental biology Metabotropic receptor Mice (Laboratory animals) RAT 030217 neurology & neurosurgery Dolor--Tractament |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona RECERCAT (Dipòsit de la Recerca de Catalunya) Recercat. Dipósit de la Recerca de Catalunya instname eLife, Vol 6 (2017) eLife eLife, 2017, 6, ⟨10.7554/elife.23545.001⟩ ResearcherID Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Digital.CSIC. Repositorio Institucional del CSIC |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.23545.001⟩ |
| Popis: | Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug’s release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders. © Font et al. This work was supported by MINECO/ISCIII (SAF2014-55700-P, PCIN-2013–019 C03-03 and PIE14/ 00034), the Catalan Government (2014 SGR 1054), ICREA (ICREA Academia-2010), Fundació la Marató de TV3 (Grant 20152031) and IWT (SBO-140028) to FC. MINECO (PCIN-2013–018 C03-02 and SAF2014-58396-R) to JG. MINECO (PCIN-2013–017 C03-01 and CTQ2014-57020-R), the Catalan Government (2014SGR109 and 2014CTP0002) to AL. ERANET Neuron project ‘LIGHTPAIN’ (to AL, JG, PC and FN). MINECO (CTQ2013-48767-C3-1-R and CTQ2015-71896-REDT), the Catalan Government (2014SGR304) to SN RB-O thanks the European Social Funds and the SUR del DEC de la Generalitat de Catalunya for a predoctoral fellowship (2016 FI_B1 00021). |
| Databáze: | OpenAIRE |
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