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Deep brain optical manipulation of endogenous receptors to modulate pain

[Speaker] Cyril Goudet:1
1:Institut de Genomique Fonctionnelle, CNRS, INSERM, Univ. Montpellier, France

Photopharmacology (also known as optopharmacology) is a novel technique allowing manipulation of the biological activity of endogenous targets with accurate spatial and temporal resolution via the use of light and small, diffusible, drug-like, photo-regulated ligands as external triggers for receptor activation or inactivation. Herein, we used photopharmacology to study regulatory mechanisms involved in persistent and chronic pain. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors responsible of the neuromodulatory effect of glutamate, the major neurotransmitter involved in the transmission of pain throughout the central nervous system. Taking advantage of novel selective photoswitchable allosteric modulators that we recently developed, we took control of mGluRs by light in the brain of freely moving animals and studied the role of these receptors in chronic pain. We demonstrated that mGluRs expressed in the amygdala, a key brain region linking pain sensation with negative emotions, can rapidly and reversibly inhibit behavioral symptoms associated to chronic pain. These findings could help to define novel and more precise therapeutic interventions for chronic pain, and exemplify the potential of in vivo photopharmacology.
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