Title:
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Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator
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Author:
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Font, Joan; López-Cano, Marc; Notartomaso, Serena; Scarselli, Pamela; Di Pietro, Paola; Bresolí-Obach, Roger; Battaglia, Giuseppe; Malhaire, Fanny; Rovira, Xavier; Catena, Juanlo; Giraldo, Jesús; Pin, Jean-Philippe; Fernández Dueñas, Víctor; Goudet, Cyril; Nonell, S. (Santi); Nicoletti, Ferdinando; Llebaria Soldevila, Amadeu; Ciruela Alférez, Francisco
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Neurociències -Ratolins (Animals de laboratori) -Farmacologia -Tractament del dolor -Neurosciences -Mice (Laboratory animals) -Pharmacology -Pain treatment |
Rights:
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cc-by (c) Font, Joan et al., 2017
http://creativecommons.org/licenses/by/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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eLife Sciences
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