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Nociception modulation by supraspinal group III metabotropic glutamate receptors
Author(s) -
Palazzo Enza,
Marabese Ida,
Luongo Livio,
Guida Francesca,
Novellis Vito,
Maione Sabatino
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13725
Subject(s) - metabotropic glutamate receptor , neuroscience , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 5 , glutamate receptor , metabotropic glutamate receptor 2 , metabotropic glutamate receptor 6 , neurotransmission , metabotropic glutamate receptor 8 , chronic pain , pharmacology , medicine , biology , receptor
The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system ( CNS ), are exerted through the activation of metabotropic glutamate receptors ( mG luRs). Of the eight known mG luRs ( mG luR1–8), group III mG luRs ( mG luR4, mG luR6, mG luR7, and mG luR8) are less understood because of the lack of selective ligands. Except for mG luR6, group III mG luRs are widely distributed throughout the CNS . They are mainly located on presynaptic terminals where they inhibit neurotransmitter release at glutamatergic and γ‐aminobutyric acid ( GABA )ergic synapses. Their location at certain synapses is considered critical for normal CNS function, which makes them potential targets in neurological and psychiatric treatments. Novel ligands that are selective for group III mG luR subtypes have recently been developed. These compounds, which mainly target allosteric sites and act as positive or negative allosteric modulators ( PAM s or NAMs) of glutamate transmission, are contributing to the understanding of the functional roles of group III mG luRs in a number of pathological conditions, such as epilepsy, anxiety, neurodegenerative diseases, and chronic pain. Moreover, the presence of group III mG luRs throughout the entire pain neuraxis and particularly in the descending system suggests that these endogenous substrates that extend from the cortex to the first spinal synapse are candidates for pain control. Recent data on chronic pain alleviation by group III mG luR ligands encourage further studies as pathological pain is one of the most troublesome diseases because of the current lack of satisfactory therapy. This review summarizes recent studies on group III mG luRs in animal models of chronic pain, which evidence an opposite modulation of mG luR7 and mG luR8 on pain responses and their capability to affect pain responses only in pathological states. This article is part of the special article series “Pain” .