Title:The Modulation of Pain by Metabotropic Glutamate Receptors 7 and 8 in the Dorsal Striatum
Volume: 18
Issue: 1
Author(s): Serena Boccella, Ida Marabese, Francesca Guida, Livio Luongo, Sabatino Maione and Enza Palazzo*
Affiliation:
- Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”, Via Costantinopoli 16, 80138 Naples,Italy
Keywords:
mGluR7, mGluR8, dorsal striatum, chronic pain, descending pain modulatory system, hyperglutamatergism.
Abstract: The dorsal striatum, apart from controlling voluntary movement, displays a recently
demonstrated pain inhibition. It is connected to the descending pain modulatory system and in particular
to the rostral ventromedial medulla through the medullary dorsal reticular nucleus. Diseases
of the basal ganglia, such as Parkinson's disease, in addition to being characterized by motor disorders,
are associated with pain and hyperactivation of the excitatory transmission. A way to counteract
glutamatergic hyperactivation is through the activation of group III metabotropic glutamate
receptors (mGluRs), which are located on presynaptic terminals inhibiting neurotransmitter release.
So far the mGluRs of group III have been the least investigated, owing to a lack of selective tools.
More recently, selective ligands for each mGluR of group III, in particular positive and negative
allosteric modulators, have been developed and the role of each subtype is starting to emerge. The
neuroprotective potential of group III mGluRs in pathological conditions, such as those characterized
by elevate glutamate, has been recently shown. In the dorsal striatum, mGluR7 and mGluR8
are located at glutamatergic corticostriatal terminals and their stimulation inhibits pain in pathological
conditions such as neuropathic pain. The two receptors in the dorsal striatum have instead a
different role in pain control in normal conditions. This review will discuss recent results focusing
on the contribution of mGluR7 and mGluR8 in the dorsal striatal control of pain. The role of
mGluR4, whose antiparkinsonian activity is widely reported, will also be addressed.