Supraspinal metabotropic glutamate receptors: An endogenous substrate for alleviating chronic pain and related affective disorders

Abstract

Metabotropic glutamate receptors (mGluRs) are key players in modulating excitatory transmission and important regulators of synaptic plasticity. mGluRs are G-protein-coupled receptors (GPCRs) that have been subdivided into three groups (mGluR1-mGluR8) based on sequence homology, intracellular pathways, and pharmacological profile. mGluRs are widely localized all along the nociceptive neuroaxis, including brain circuits controlling pain often overlapping those controlling affective/cognitive behaviors which prove deeply altered in several neurological disorders including chronic pain. This chapter summarizes current outcomes related to the supraspinal mGluRs in chronic pain states. Due to their wide expression within the pain descending system, a particular highlighting will be given to the pharmacological manipulation of mGluRs in PAG-RVM pathway, a key circuitry of the pain descending system. The current development of novel subtype-selective mGluR positive and negative allosteric modulators will allow a more stringent assessment of each mGluR subtype role in controlling chronic pain and pain-related affective cognitive behavior.