Glutamate is the main excitatory neurotransmitter of the mammalian central nervous system. As a result, glutamate neurotransmission is involved in many physiological and pathophysiological processes. Glutamate exerts its action through activation of two broad classes of receptors: ionotropic and metabotropic G-protein coupled receptors.

Metabotropic glutamate receptors (mGluRs) have been shown to regulate nociceptive signalling at different levels of the nervous system. While the role of group I and II mGluRs in pain is now well documented, less is known on group III mGluRs due in part to the lack of specific pharmacology for these receptors.

Recently, we and others have shown that spinal group-III metabotropic glutamate receptors activation reduced hyperalgesia in different animal models of neuropathy and inflammation, while acute pain perception remained unchanged in healthy animals. Agonists of these receptors thus appear as promising new therapeutic agents to treat neuropathic or inflammatory pain.

This talk will present our efforts to improve the pharmacological toolbox of these receptors by the development of new ligands in order to reinforce the evidences of group III mGluRs involvement in pain modulation and ideally validate these receptors as therapeutic target to treat chronic pain.