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Supraspinal Metabotropic Glutamate Receptors: An Endogenous Substrate for Alleviating Chronic Pain and Related Affective Disorders

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mGLU Receptors

Part of the book series: The Receptors ((REC,volume 31))

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.

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Abbreviations

BLA:

basolateral amygdala

CeA:

central nucleus of the amygdala

CNS:

central nervous system

CPCCOEt:

7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester

(S)-3,4-DCPG:

(S)-3,4-dicarboxyphenylglycine

GPCRs:

G-protein coupled receptors

iGluR:

ionotropic glutamate receptor

IL:

infra-limbic

mGluR:

metabotropic glutamate receptor

MPEP:

2-methyl-6-(phenylethynyl)pyridine

mPFC:

medial prefrontal cortex

NAAG:

N-acetylaspartylglutamate

NMDA:

N-methyl-D-aspartate

NTS:

nucleus tractus solitarius

PAG:

periaqueductal gray

PL:

pre-limbic

PLC:

phospholipase C

RVM:

rostral ventromedial medulla

TRPV1:

transient receptor potential vanilloid 1

References

  • Acher F, Goudet C (2015) Therapeutic potential of group III metabotropic glutamate receptor ligands in pain. Curr Opin Pharmacol 20:64–72

    Article  CAS  PubMed  Google Scholar 

  • Attwell PJE, Kaura S, Sigala G, Bradford HF, Croucher MJ, Jane DE et al (1995) Blockade of both epileptogenesis and glutamate release by (1S,3S)-ACPD, a presynaptic glutamate receptor agonist. Brain Res 698(1–2):155–162

    Article  CAS  PubMed  Google Scholar 

  • Battaglia G, Monn JA, Schoepp DD (1997) In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats. Neurosci Lett 229(3):161–164

    Article  CAS  PubMed  Google Scholar 

  • Behbehani MM (1995) Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 46(6):575–605

    Article  CAS  PubMed  Google Scholar 

  • Behbehani MM, Fields HL (1979) Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia. Brain Res 170(1):85–93

    Article  CAS  PubMed  Google Scholar 

  • Berrino L, Oliva P, Rossi F, Palazzo E, Nobili B, Maione S (2001) Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system. Naunyn Schmiedebergs Arch Pharmacol 364(5):437–443

    Article  CAS  PubMed  Google Scholar 

  • Bhave G, Karim F, Carlton SM, Gereau RW (2001) Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci 4(4):417–423

    Article  CAS  PubMed  Google Scholar 

  • Bleakman D, Lodge D (1998) Neuropharmacology of AMPA and kainate receptors. Neuropharmacol 37(10–11):1187–1204

    Article  CAS  Google Scholar 

  • Borszcz GS, Leaton RN (2003) The effect of amygdala lesions on conditional and unconditional vocalizations in rats. Neurobiol Learn Mem 79(3):212–225

    Article  PubMed  Google Scholar 

  • Byrnes KR, Stoica B, Loane DJ, Riccio A, Davis MI, Faden AI (2009) Metabotropic glutamate receptor 5 activation inhibits microglial associated inflammation and neurotoxicity. Glia. 57(5):550–560

    Article  PubMed  PubMed Central  Google Scholar 

  • Carlton SM, Du J, Zhou S (2009) Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 function. Brain Res 1248:86–95

    Article  CAS  PubMed  Google Scholar 

  • Carrasquillo Y, Gereau RW (2008) Hemispheric lateralization of a molecular signal for pain modulation in the amygdala. Mol Pain 4:24

    Article  PubMed  PubMed Central  Google Scholar 

  • Cartmell J, Schoepp DD (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 75(3):889–907

    Article  CAS  PubMed  Google Scholar 

  • Catania MV, De SH, Penney JB, Young AB (1994) Metabotropic glutamate receptor heterogeneity in rat brain. Mol Pharmacol 45(4):626–636

    CAS  PubMed  Google Scholar 

  • Chiechio S, Nicoletti F (2012) Metabotropic glutamate receptors and the control of chronic pain. Curr Opin Pharmacol. 12(1):28–34

    Article  CAS  PubMed  Google Scholar 

  • Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain. 87(2):149–158

    Article  CAS  PubMed  Google Scholar 

  • Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326(2):483–504

    Article  CAS  PubMed  Google Scholar 

  • Fields HL, Basbaum AI (1999) Central nervous system mechanisms of pain modulation. In: Wall PD, Melzack R (eds) Textbook of pain. Churchill Livingstone, New York, pp 243–257

    Google Scholar 

  • Fields HL, Bry J, Hentall I, Zorman G (1983) The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 3(12):2545–2552

    CAS  PubMed  Google Scholar 

  • Gerber G, Zhong J, Youn D, Randic M (2000) Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn. Neurosci. 100(2):393–406

    Article  CAS  Google Scholar 

  • Giordano C, Cristino L, Luongo L, Siniscalco D, Petrosino S, Piscitelli F et al (2012) TRPV1-dependent and-independent alterations in the limbic cortex of neuropathic mice: impact on glial caspases and pain perception. Cereb Cortex. 22(11):2495–2518

    Article  PubMed  Google Scholar 

  • Goudet C, Chapuy E, Alloui A, Acher F, Pin JP, Eschalier A (2008) Group III metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain. Pain. 137(1):112–124

    Article  CAS  PubMed  Google Scholar 

  • Guida F, Luongo L, Marmo F, Romano R, Iannotta M, Napolitano F, Belardo C, Marabese I, D’Aniello A, Bellini G, Rossi F, Piscitelli F, Lattanzi R, de Bartolomeis A, Usiello A, Di Marzo V, de Novellis V, Maione S (2015) Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice. Mol Brain 8:47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hama AT (2003) Acute activation of the spinal cord metabotropic glutamate subtype-5 receptor leads to cold hypersensitivity in the rat. Neuropharmacology 44(4):423–430

    Article  CAS  PubMed  Google Scholar 

  • Han JS, Neugebauer V (2005) mGluR1 and mGluR5 antagonists in the amygdala inhibit different components of audible and ultrasonic vocalizations in a model of arthritic pain. Pain 113(1–2):211–222

    Article  CAS  PubMed  Google Scholar 

  • Han JS, Bird GC, Neugebauer V (2004) Enhanced group III mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala. Neuropharmacology 46(7):918–926

    Article  CAS  PubMed  Google Scholar 

  • Heinricher MM, Barbaro NM, Fields HL (1989) Putative nociceptive modulating neurons in the rostral ventromedial medulla of the rat: firing of on- and off-cells is related to nociceptive responsiveness. Somatosens Mot Res 6(4):427–439

    Article  CAS  PubMed  Google Scholar 

  • Hu H-J, Bhave G, Gereau RW (2002) Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia. J Neurosci. 22(17):7444–7452

    CAS  PubMed  Google Scholar 

  • Hung KL, Wang SJ, Wang YC, Chiang TR, Wang CC (2014) Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain. Pain. 155(2):377–387

    Article  CAS  PubMed  Google Scholar 

  • Ji G, Neugebauer V (2010) Reactive oxygen species are involved in group I mGluR-mediated facilitation of nociceptive processing in amygdala neurons. J Neurophysiol 104(1):218–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji G, Neugebauer V (2011) Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors. J Neurophysiol 106(5):2642–2652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones CK, Eberle EL, Peters SC, Monn JA, Shannon HE (2005) Analgesic effects of the selective group II (mGlu2/3) metabotropic glutamate receptor agonists LY379268 and LY389795 in persistent and inflammatory pain models after acute and repeated dosing. Neuropharmacology 49(Suppl):206–218

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Cui L, Kim J, Kim SJ (2009) Transient receptor potential vanilloid type 1 receptor regulates glutamatergic synaptic inputs to the spinothalamic tract neurons of the spinal cord deep dorsal horn. Neuroscience 160(2):508–516

    Article  CAS  PubMed  Google Scholar 

  • Kinoshita A, Shigemoto R, Ohishi H, van der Putten H, Mizuno N (1998) Immunohistochemical localization of metabotropic glutamate receptors, mGluR7a and mGluR7b, in the central nervous system of the adult rat and mouse: a light and electron microscopic study. J Comp Neurol 393(3):332–352

    Article  CAS  PubMed  Google Scholar 

  • Kinzie JM, Saugstad JA, Westbrook GL, Segerson TP (1995) Distribution of metabotropic glutamate receptor 7 messenger RNA in the developing and adult rat brain. Neuroscience 69(1):167–176

    Article  CAS  PubMed  Google Scholar 

  • Kolber BJ, Montana MC, Carrasquillo Y, Xu J, Heinemann SF, Muglia LJ et al (2010) Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. J Neurosci 30(24):8203–8213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926

    Article  PubMed  PubMed Central  Google Scholar 

  • Leyva J, Maione S, Pallotta M, Berrino L, Rossi F (1995) Metabotropic and ionotropic glutamate receptors mediate opposite effects on periaqueductal gray matter. Eur J Pharmacol 285(2):123–126

    Article  CAS  PubMed  Google Scholar 

  • Li W, Neugebauer V (2006) Differential changes of group II and group III mGluR function in central amygdala neurons in a model of arthritic pain. J Neurophysiol 96(4):1803–1815

    Article  CAS  PubMed  Google Scholar 

  • Linden AM, Shannon H, Baez M, Yu JL, Koester A, Schoepp DD (2005) Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice. Psychopharmacology 179(1):284–291

    Article  CAS  PubMed  Google Scholar 

  • Linden A-M, Baez M, Bergeron M, Schoepp DD (2006) Effects of mGlu2 or mGlu3 receptor deletions on mGlu2/3 receptor agonist (LY354740)-induced brain c-Fos expression: specific roles for mGlu2 in the amygdala and subcortical nuclei, and mGlu3 in the hippocampus. Neuropharmacology 51(2):213–228

    Article  CAS  PubMed  Google Scholar 

  • Liu XH, Han M, Zhu JX, Sun N, Tang JS, Huo FQ et al (2012) Metabotropic glutamate subtype 7 and 8 receptors oppositely modulate cardiac nociception in the rat nucleus tractus solitarius. Neuroscience [Internet] 220:322–329

    Article  CAS  Google Scholar 

  • Luongo L, De Novellis V, Gatta L, Palazzo E, Vita D, Guida F et al (2013) Role of metabotropic glutamate receptor 1 in the basolateral amygdala-driven prefrontal cortical deactivation in inflammatory pain in the rat. Neuropharmacology 66:317–329

    Article  CAS  PubMed  Google Scholar 

  • Maione S, Palazzo E, de Novellis V et al (1998a) Metabotropic glutamate receptors modulate serotonin release in the rat periaqueductal gray matter. Naunyn Schmiedebergs Arch Pharmacol 358(4):411–417

    Article  CAS  PubMed  Google Scholar 

  • Maione S, Marabese I, Leyva J, Palazzo E, De Novellis V, Rossi F (1998b) Characterisation of mGluRs which modulate nociception in the PAG of the mouse. Neuropharmacology 37(12):1475–1483

    Article  CAS  PubMed  Google Scholar 

  • Maione S, Oliva P, Marabese I, Palazzo E, Rossi F, Berrino L et al (2000) Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception. Pain 85(1–2):183–189

    Article  CAS  PubMed  Google Scholar 

  • Marabese I, de Novellis V, Palazzo E, Mariani L, Siniscalco D, Rodella L et al (2005) Differential roles of mGlu8 receptors in the regulation of glutamate and gamma-aminobutyric acid release at periaqueductal grey level. Neuropharmacology 1:157–166

    Article  Google Scholar 

  • Marabese I, de Novellis V, Palazzo E, Scafuro MA, Vita D, Rossi F et al (2007a) Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice. Neuropharmacology 52(2):253–262

    Article  CAS  PubMed  Google Scholar 

  • Marabese I, Rossi F, Palazzo E, de Novellis V, Starowicz K, Cristino L et al (2007b) 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 98(1):43–53

    Article  CAS  PubMed  Google Scholar 

  • Mitsukawa K, Yamamoto R, Ofner S, Nozulak J, Pescott O, Lukic S, Stoehr N, Mombereau C, Kuhn R, KH MA, van der Putten H, Cryan JF, Flor PJ (2005) A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Proc Natl Acad Sci USA 102:18712–18717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura M, Kurihara H, Suzuki G, Mitsuya M, Ohkubo M, Ohta H (2010) Isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists. Bioorganic Med Chem Lett. 20(2):726–729

    Article  CAS  Google Scholar 

  • Neto FL, Castro-Lopes JM (2000) Antinociceptive effect of a group II metabotropic glutamate receptor antagonist in the thalamus of monoarthritic rats. Neurosci Lett. 296(1):25–28

    Article  CAS  PubMed  Google Scholar 

  • Neto FL, Schadrack J, Berthele A, Zieglgänsberger W, Tölle TR, Castro-Lopes JM (2000) Differential distribution of metabotropic glutamate receptor subtype mRNAs in the thalamus of the rat. Brain Res 854(1–2):93–105

    Article  Google Scholar 

  • Neugebauer V (2001) Metabotropic glutamate receptors: novel targets for pain relief. Expert Rev Neurother 1(2):207–224

    Article  CAS  PubMed  Google Scholar 

  • Neugebauer V, Li W, Bird GC, Bhave G, Gereau RW (2003a) Synaptic plasticity in the amygdala in a model of arthritic pain: differential roles of metabotropic glutamate receptors 1 and 5. J Neurosci 23(1):52–63

    CAS  PubMed  Google Scholar 

  • Neugebauer V, Galhardo V, Maione S, Mackey SC (2009) Forebrain pain mechanisms. Brain Res Rev 60(1):226–242

    Article  PubMed  Google Scholar 

  • Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohishi H, Akazawa C, Shigemoto R, Nakanishi S, Mizuno N (1995) Distributions of the mRNAs for L-2-amino-4- phosphonobutyrate-sensitive metabotropic glutamate receptors, mGluR4 and mGluR7, in the rat brain. J Comp Neurol 360(4):555–570

    Article  CAS  PubMed  Google Scholar 

  • Palazzo E, Marabese I, De Novellis V, Oliva P, Rossi F, Berrino L et al (2001) Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception. Neuropharmacology 40(3):319–326

    Article  CAS  PubMed  Google Scholar 

  • Palazzo E, De Novellis V, Marabese I, Cuomo D, Rossi F, Berrino L et al (2002) Interaction between vanilloid and glutamate receptors in the central modulation of nociception. Eur J Pharmacol 439(1–3):69–75

    Article  CAS  PubMed  Google Scholar 

  • Palazzo E, Genovese R, Mariani L, Siniscalco D, Marabese I, De Novellis V et al (2004) Metabotropic glutamate receptor 5 and dorsal raphe serotonin release in inflammatory pain in rat. Eur J Pharmacol 492(2–3):169–176

    Article  CAS  PubMed  Google Scholar 

  • Palazzo E, Marabese I, Soukupova M, Luongo L, Boccella S, Giordano C et al (2011b) Metabotropic glutamate receptor subtype 8 in the amygdala modulates thermal threshold, neurotransmitter release, and rostral ventromedial medulla cell activity in inflammatory pain. J Neurosci 31(12):4687–4697

    Article  CAS  PubMed  Google Scholar 

  • Palazzo E, Luongo L, Bellini G, Guida F et al (2012) Changes in Cannabinoid Receptor Subtype 1 Activity and Interaction with Metabotropic Glutamate Subtype 5 Receptors in the Periaqueductal Gray-Rostral Ventromedial Medulla Pathway in a Rodent Neuropathic Pain Model. CNS Neurol Disord Drug Targets 11(2)

    Google Scholar 

  • Palazzo E, Marabese I, de Novellis V, Rossi F, Maione S (2014a) Supraspinal metabotropic glutamate receptors: a target for pain relief and beyond. Eur J Neurosci. 39(3):444–454

    Article  PubMed  Google Scholar 

  • Palazzo E, de Novellis V, Rossi F, Maione S (2014b) Supraspinal metabotropic glutamate receptor subtype 8: a switch to turn off pain. Amino Acids 46(6):1441–1448

    CAS  PubMed  Google Scholar 

  • Palazzo E, Romano R, Luongo L, Boccella S, De Gregorio D, Giordano ME et al (2015) MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice. Pain 156(6):1060–1073

    CAS  PubMed  Google Scholar 

  • Ren W, Neugebauer V (2010) Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1. Mol Pain 6:93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reynolds DV (1969) Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 164(878):444–445

    Article  CAS  PubMed  Google Scholar 

  • Rossi F, Marabese I, De Chiaro M, Boccella S, Luongo L, Guida F et al (2014) Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions. J Neurophysiol 111(11):2196–2209

    Article  CAS  PubMed  Google Scholar 

  • Salt TE, Binns KE (2000) Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-D-aspartate receptor-mediated responses and nociceptive sensory responses of rat thalamic neurons. Neuroscience 100(2):375–380

    Article  CAS  PubMed  Google Scholar 

  • Salt TE, Eaton SA (1995) Modulation of sensory neurone excitatory and inhibitory responses in the ventrobasal thalamus by activation of metabotropic excitatory amino acid receptors. Neuropharmacology 34(8):1043–1051

    Article  CAS  PubMed  Google Scholar 

  • Salt TE, Turner JP (1998) Modulation of sensory inhibition in the ventrobasal thalamus via activation of group II metabotropic glutamate receptors by 2R,4R-aminopyrrolidine-2,4-dicarboxylate. Exp Brain Res 121(2):181–185

    Article  CAS  PubMed  Google Scholar 

  • Saugstad JA, Kinzie JM, Shinohara MM, Segerson TP, Westbrook GL (1997) Cloning and expression of rat metabotropic glutamate receptor 8 reveals a distinct pharmacological profile. Mol Pharmacol 51(1):119–125

    CAS  PubMed  Google Scholar 

  • Saugstad JA, Marino MJ, Folk JA, Hepler JR, Conn PJ (1998) RGS4 inhibits signaling by group I metabotropic glutamate receptors. J Neurosci 18(3):905–913

    CAS  PubMed  Google Scholar 

  • Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299(1):12–20

    CAS  PubMed  Google Scholar 

  • Spaziano G, Luongo L, Guida F, Petrosino S, Matteis M, Palazzo E et al (2015) Exposure to allergen causes changes in NTS neural activities after intratracheal capsaicin application, in endocannabinoid levels and in the glia morphology of NTS. Biomed Res Int 2015:980983

    Article  PubMed  PubMed Central  Google Scholar 

  • Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H et al (2007) In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists. J Pharmacol Exp Ther 323(1):147–156

    Article  CAS  PubMed  Google Scholar 

  • Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE (2001) (S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord. Neuropharmacology 40(3):311–318

    Article  CAS  PubMed  Google Scholar 

  • Tian Y, Liu Y, Chen X, Kang Q, Zhang J, Shi Q et al (2010) AMN082 promotes the proliferation and differentiation of neural progenitor cells with influence on phosphorylation of MAPK signaling pathways. Neurochem Int 57(1):8–15

    Article  CAS  PubMed  Google Scholar 

  • Turner JP, Salt TE (1999) Group III metabotropic glutamate receptors control corticothalamic synaptic transmission in the rat thalamus in vitro. JPhysiol 519:481–491

    CAS  Google Scholar 

  • Urban MO, Hama AT, Bradbury M, Anderson J, Varney MA, Bristow L (2003) Role of metabotropic glutamate receptor subtype 5 (mGluR5) in the maintenance of cold hypersensitivity following a peripheral mononeuropathy in the rat. Neuropharmacology 44(8):983–993

    Article  CAS  PubMed  Google Scholar 

  • Vardi N, Duvoisin R, Wu G, Sterling P (2000) Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J Comp Neurol 423(3):402–412

    Article  CAS  PubMed  Google Scholar 

  • Veinante P, Yalcin I, Barrot M (2013) The amygdala between sensation and affect: a role in pain. J Mol Psychiat 1(1):9

    Article  Google Scholar 

  • Walker K, Reeve A, Bowes M, Winter J, Wotherspoon G, Davis A et al (2000) mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia. Neuropharmacology 40(1):10–19

    Article  Google Scholar 

  • Yamada T, Zuo D, Yamamoto T, Olszewski RT, Bzdega T, Moffett JR, Neale JH (2012) Peptidase inhibition in the periaqueductal gray and rostral ventromedial medulla reduces flinching in the formalin model inflammation. Mol Pain 12:8–67

    Google Scholar 

  • Yamakura T, Shimoji K (1999) Subunit- and site-specific pharmacology of the NMDA receptor channel. Prog Neurobiol 59(3):279–298

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Kozikowski A, Zhou J, Neale JH (2000) Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain. Mol Pain 81:4–31

    Google Scholar 

  • Yang D, Gereau RW (2002) Peripheral group II metabotropic glutamate receptors (mGluR2/3) regulate prostaglandin E2-mediated sensitization of capsaicin responses and thermal nociception. J Neurosci. 22(15):6388–6393

    CAS  PubMed  Google Scholar 

  • Yang D, Gereau RW (2003) Peripheral group II metabotropic glutamate receptors mediate endogenous anti-allodynia in inflammation. Pain:411–417

    Google Scholar 

  • Zammataro M, Chiechio S, Montana MC, Traficante A, Copani A, Nicoletti F et al (2011) mGlu2 metabotropic glutamate receptors restrain inflammatory pain and mediate the analgesic activity of dual mGlu2/mGlu3 receptor agonists. Mol Pain 7:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Università degli Studi della Campania “Luigi Vanvitelli”, 80138, Naples, Italy

    Francesca Guida Ph.D., Enza Palazzo Ph.D., Livio Luongo Ph.D., Ida Marabese Ph.D., Vito de Novellis Ph.D., Sabatino Maione Ph.D. & Francesco Rossi Ph.D.

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  1. Francesca Guida Ph.D.
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  2. Enza Palazzo Ph.D.
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  3. Livio Luongo Ph.D.
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  4. Ida Marabese Ph.D.
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  5. Vito de Novellis Ph.D.
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  6. Sabatino Maione Ph.D.
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  7. Francesco Rossi Ph.D.
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Correspondence to Sabatino Maione Ph.D. .

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  1. Neuropharmacology Unit I.N.M. Neuromed, I.N.M. Neuromed, Pozzilli, Isernia, Italy

    Richard Teke Ngomba

  2. Department of Physiology and Biochemistry, University of Malta, Malta, Italy

    Giuseppe Di Giovanni

  3. Neuropharmacology Unit, I.N.M. Neuromed, Pozzilli, Isernia, Italy

    Giuseppe Battaglia

  4. Dipartimento di Fisiologia Umana, Università di Roma, Roma, Italy

    Ferdinando Nicoletti

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Guida, F. et al. (2017). Supraspinal Metabotropic Glutamate Receptors: An Endogenous Substrate for Alleviating Chronic Pain and Related Affective Disorders. In: Ngomba, R., Di Giovanni, G., Battaglia, G., Nicoletti, F. (eds) mGLU Receptors. The Receptors, vol 31. Humana Press, Cham. https://doi.org/10.1007/978-3-319-56170-7_2

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