About this Research Topic
Metabotropic glutamate receptors (mGluRs) modulate excitatory neurotransmission, and thus are important regulators of synapses in the CNS. mGluRs (mGluR1-mGluR8) are G-protein coupled receptors (GPCRs) subdivided into three groups (I-III) based on sequence homology, transductional pathways, and pharmacological profile. They are widely localized along the pain neuraxis from sensory afferent neuron terminals, dorsal root ganglia, and the spinal cord dorsal horn to supraspinal structures such as the periaqueductal grey, thalamus, amygdala, and cortex. Thus, mGluRs are strategically positioned within neural circuits controlling pain, and often overlap with those controlling affective/cognitive behaviors.
This pattern of expression is particularly suitable as a substrate for designing novel agents against pain and emotional disorders, these latter showing wide co-morbidity with chronic pain. Among mGluRs, those of Group III (mGluR4, mGluR6, mGluR7, and mGluR8) are less defined due to the lack of selective ligands. Excepting mGluR6, Group III mGluRs are widely distributed throughout the CNS at presynaptic terminals, where they inhibit neurotransmitter release at glutamatergic and γ-aminobutyric acid (GABA)ergic synapses. Novel selective and brain penetrable ligands for Group III mGluR subtypes have been recently developed that mainly target allosteric sites, acting as positive or negative allosteric modulators (PAMs or NAMs) of glutamate transmission. These compounds contribute to the understanding of the functional roles of Group III mGluRs in a number of pathological conditions, such as epilepsy, anxiety, neurodegenerative diseases, and chronic pain.
This Research Topic will address the most recent findings on mGluRs, with particular emphasis on Group III mGluRs, whose modulation of glutamatergic transmission has a great impact on synapse functioning and neural plasticity at the base of neurological and psychiatric disorders. The overlapping of neural substrates, neurotransmitters, and mechanisms of some neurological and psychiatric disorders--such as chronic pain and affective/cognitive deficits--may represent symptoms of the same disease more than co-morbidities, due to a cause-effect relationship.
Keywords: Central nervous system, metabotropic glutamate receptors, chronic pain, pain-related emotional disorders, allosteric modulators
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