The Modulation of Pain by Metabotropic Glutamate Receptors 7 and 8 in the Dorsal Striatum

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2019 Jun 19

PMID 31210112

Citations 12

Authors

Serena Boccella

Ida Marabese

Francesca Guida

Livio Luongo

Sabatino Maione

Enza Palazzo

Affiliations

Soon will be listed here.

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.

Citing Articles

Pain in Parkinson's disease: a neuroanatomy-based approach.

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GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients.

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Li J, Wang Y, Yang R, Ma W, Yan J, Li Y Front Aging Neurosci. 2023; 15:1190563.

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References

Albin R, Young A, Penney J . The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989; 12(10):366-75. DOI: 10.1016/0166-2236(89)90074-x. View

Charvin D, Pomel V, Ortiz M, Frauli M, Scheffler S, Steinberg E . Discovery, Structure-Activity Relationship, and Antiparkinsonian Effect of a Potent and Brain-Penetrant Chemical Series of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4. J Med Chem. 2017; 60(20):8515-8537. DOI: 10.1021/acs.jmedchem.7b00991. View

Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H . In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists. J Pharmacol Exp Ther. 2007; 323(1):147-56. DOI: 10.1124/jpet.107.124701. View

Gerlai R, Roder J, Hampson D . Altered spatial learning and memory in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. Behav Neurosci. 1998; 112(3):525-32. DOI: 10.1037//0735-7044.112.3.525. View

Pelkey K, Yuan X, Lavezzari G, Roche K, McBain C . mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082. Neuropharmacology. 2006; 52(1):108-17. DOI: 10.1016/j.neuropharm.2006.07.020. View

Bell M, Richardson P, Lee K . Functional and molecular characterization of metabotropic glutamate receptors expressed in rat striatal cholinergic interneurones. J Neurochem. 2002; 81(1):142-9. DOI: 10.1046/j.1471-4159.2002.00815.x. View

Marabese I, Rossi F, Palazzo E, de Novellis V, Starowicz K, Cristino L . Periaqueductal gray metabotropic glutamate receptor subtype 7 and 8 mediate opposite effects on amino acid release, rostral ventromedial medulla cell activities, and thermal nociception. J Neurophysiol. 2007; 98(1):43-53. DOI: 10.1152/jn.00356.2007. View

Bogenpohl J, Galvan A, Hu X, Wichmann T, Smith Y . Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex. Neuropharmacology. 2012; 66:242-52. PMC: 3490034. DOI: 10.1016/j.neuropharm.2012.05.017. View

Palazzo E, Marabese I, de Novellis V, Rossi F, Maione S . Supraspinal metabotropic glutamate receptors: a target for pain relief and beyond. Eur J Neurosci. 2014; 39(3):444-54. DOI: 10.1111/ejn.12398. View

10.

Betts M, ONeill M, Duty S . Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease. Br J Pharmacol. 2012; 166(8):2317-30. PMC: 3448896. DOI: 10.1111/j.1476-5381.2012.01943.x. View

11.

Schoepp D . Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther. 2001; 299(1):12-20. View

12.

Thomsen C . The L-AP4 receptor. Gen Pharmacol. 1997; 29(2):151-8. DOI: 10.1016/s0306-3623(96)00417-x. View

13.

Crawley J . Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res. 1999; 835(1):18-26. DOI: 10.1016/s0006-8993(98)01258-x. View

14.

Gerlai R, Adams B, Fitch T, Chaney S, Baez M . Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype. Neuropharmacology. 2002; 43(2):235-49. DOI: 10.1016/s0028-3908(02)00078-3. View

15.

Rovira X, Trapero A, Pittolo S, Zussy C, Faucherre A, Jopling C . OptoGluNAM4.1, a Photoswitchable Allosteric Antagonist for Real-Time Control of mGlu4 Receptor Activity. Cell Chem Biol. 2016; 23(8):929-34. DOI: 10.1016/j.chembiol.2016.06.013. View

16.

Kinoshita A, Ohishi H, Nomura S, Shigemoto R, Nakanishi S, Mizuno N . Presynaptic localization of a metabotropic glutamate receptor, mGluR4a, in the cerebellar cortex: a light and electron microscope study in the rat. Neurosci Lett. 1996; 207(3):199-202. DOI: 10.1016/0304-3940(96)12519-2. View

17.

Bahi A . The pre-synaptic metabotropic glutamate receptor 7 "mGluR7" is a critical modulator of ethanol sensitivity in mice. Neuroscience. 2011; 199:13-23. DOI: 10.1016/j.neuroscience.2011.10.029. View

18.

Mercier M, Lodge D, Fang G, Nicolas C, Collett V, Jane D . Characterisation of an mGlu8 receptor-selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus. Neuropharmacology. 2012; 67:294-303. DOI: 10.1016/j.neuropharm.2012.11.020. View

19.

Mitsukawa K, Yamamoto R, Ofner S, Nozulak J, Pescott O, Lukic S . A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Proc Natl Acad Sci U S A. 2005; 102(51):18712-7. PMC: 1317946. DOI: 10.1073/pnas.0508063102. View

20.

Kravitz A, Freeze B, Parker P, Kay K, Thwin M, Deisseroth K . Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466(7306):622-6. PMC: 3552484. DOI: 10.1038/nature09159. View