Font, JoanLópez-Cano, MarcNotartomaso, SerenaScarselli, PamelaDi Pietro, PaolaBresolí-Obach, RogerBattaglia, GiuseppeMalhaire, FannyRovira, XavierCatena, JuanloGiraldo, JesúsPin, Jean-PhilippeFernández Dueñas, VíctorGoudet, CyrilNonell, SantiNicoletti, FerdinandoLlebaria Soldevila, AmadeuCiruela Alférez, Francisco2018-05-252018-05-252017-04-112050-084Xhttps://hdl.handle.net/2445/122570Light-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.20 p.application/pdfengcc-by (c) Font, Joan et al., 2017http://creativecommons.org/licenses/by/3.0/esNeurociènciesRatolins (Animals de laboratori)FarmacologiaTractament del dolorNeurosciencesMice (Laboratory animals)PharmacologyPain treatmentinfo:eu-repo/semantics/article6794412018-05-25info:eu-repo/semantics/openAccess28395733