Metabotropic glutamate receptors and the control of chronic pain

Over the past two decades metabotropic glutamate (mGlu) receptor ligands have been investigated for their potential therapeutic effects in different disorders of the central nervous system (CNS), including anxiety, depression, schizophrenia, and neurodegenerative diseases. In addition, it has been widely demonstrated that mGlu receptors are able to modulate pain transmission both in inflammatory and neuropathic pain models. A large number of preclinical studies combining the use of selective ligands with the knockout strategy have revealed more details about the role of the different mGlu receptor subtypes in the modulation of pain information. This review will address the role of mGlu receptors in pain sensitivity focusing on different strategies to achieve pain control by targeting specific mGlu receptor subtypes. Specifically, pharmacological interventions aimed at inhibiting group I mGlu receptor-mediated signaling and/or potentiating groups II and Ill mGlu receptor signaling together with an epigenetic approach leading to an increased expression of mGlu2 receptors will be discussed.