Serena Notartomaso, Nico Antenucci, Mariacristina Mazzitelli, Xavier Rovira, Serena Boccella, Flavia Ricciardi, Francesca Liberatore, Xavier Gomez-Santacana, Tiziana Imbriglio, Milena Cannella, Charleine Zussy, Livio Luongo, Sabatino Maione, Cyril Goudet, Giuseppe Battaglia, Amadeu Llebaria, Ferdinando Nicoletti, Volker Neugebauer
Knowing the site of drug action is important to optimize effectiveness and address any side effects. We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical activation of systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) of mGlu5 receptors, in cingulate, prelimbic and infralimbic cortices and thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment of alloswitch-1, an intrinsically active mGlu5 receptor NAM, caused analgesia, and the effect was reversed by light-induced drug inactivation in in the prelimbic and infralimbic cortices, and thalamus...
January 3, 2024: bioRxiv