Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice

Marabese, Ida; Novellis, Vito de; Palazzo, Enza; Scafuro, Marika; Vita, Daniela De; Rossi, Francesco; Maione, Sabatino

doi:10.1016/j.neuropharm.2006.04.006

Cited by 56 publications

(58 citation statements)

References 35 publications

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“…However both of these compounds also profoundly decrease motor activity, which suggests that any effects on ethanol self-administration and relapse may be secondary to motor inhibition. The mGluR7 (group III) agonist AMN082, which was used in the present study, has also been shown to decrease glutamate by a pre-synaptic mechanism (Marabese et al, 2007). Our results show that AMN082 produces a dose-dependent reduction in ethanol self-administration of inbred C57BL/6J mice.…”

Section: Discussionsupporting

confidence: 57%

Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082

Salling

Faccidomo

Hodge

2008

Pharmacology Biochemistry and Behavior

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Emerging evidence indicates that specific metabotropic glutamate receptors (mGluRs) modulate ethanol self-administration. In general, inhibition of glutamate transmission through blockade of postsynaptic mGluRs, or activation of presynaptic mGluRs, inhibits ethanol self-administration. The goal of this preclinical study was to further characterize mGluR regulation of ethanol selfadministration by examining effects of AMN082, an allosteric positive modulator of presynaptic mGluR7 activity. Separate groups of C57BL/6J male mice were trained to self-administer ethanol or sucrose on a fixed-ratio 4 schedule of reinforcement during 1 hour sessions. On test days, mice were pretreated with AMN082 (0, 1.0, 3.0, 5.6, or 10 mg/kg) 30 minutes prior to self-administration sessions. Functional specificity and activity was examined by testing the effects of AMN082 (0 -10 mg/kg) on open-field locomotor activity and HPA axis function as measured by plasma corticosterone levels. AMN082 (10 mg/kg) produced a significant reduction in ethanol and sucrose reinforced responding, and inhibited locomotor activity. Plasma corticosterone levels were significantly increased following AMN082 (5.6 and 10 mg/kg) suggesting a dose-dependent dissociation between the behavioral and hormonal effects of the compound. These data suggest that activation of mGluR7 by AMNO82 produces non-specific reductions in motivated behavior that are associated with negative effects on motor activity.

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Section: Discussionsupporting

confidence: 57%

Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082

Salling

Faccidomo

Hodge

2008

Pharmacology Biochemistry and Behavior

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“…Moreover, ( S)-3,4-DCPG induced antinociception in several pain models, either when systemically or intra-PAG administered (Marabese et al, 2007a). In particular, intra-PAG mGluR8 stimulation determined: (1) an increase in glutamate and a decrease in GABA, antagonized by MSOP ; (2) RVM (Marabese et al, 2007b).…”

Section: Discussionmentioning

confidence: 95%

“…At this level, stimulation of metabotropic glutamate 8 receptor (mGluR8) by ( S) , a selective mGluR8 agonist (Schmid and Fendt, 2006), has instead been shown to have antinociceptive and anxiolytic properties in the arthritis pain model (Palazzo et al, 2008). As well as in the CeA, an antinociceptive effect due to mGluR8 stimulation by ( S) -3,4-DCPG has also been found within the periaqueductal gray (PAG) in inflammatory and neuropathic pain models (Marabese et al, 2007a). It has been shown that ( S)-3,4-DCPG increases glutamate and decreases GABA release consis-tently with PAG-antinociceptive descending system activation and consequent antinociception.…”

Section: Introductionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 8 in the Amygdala Modulates Thermal Threshold, Neurotransmitter Release, and Rostral Ventromedial Medulla Cell Activity in Inflammatory Pain

Palazzo

Marabese²,

Soukupová³

et al. 2011

J. Neurosci.

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The amygdala is a crucial area in controlling the threshold of pain and its emotional component. The present study has evaluated the effect of a metabotropic glutamate 8 receptor (mGluR8) stimulation in the central nucleus of the amygdala (CeA) on the thermoceptive threshold and on CeA serotonin (5-HT), glutamate (Glu), and GABA release in normal and carrageenan-induced inflammatory pain conditions in rats. Furthermore, the activity of rostral ventromedial medulla (RVM) putative "pronociceptive" ON and "antinociceptive" OFF cells has been evaluated. (S)-3,4-Dicarboxyphenylglycine [(S)-3,4-DCPG], a selective mGluR8 agonist, administered into the CeA, did not change 5-HT, Glu, and GABA release, or the thermoceptive threshold, nor did it modify the activity of ON and OFF cells of the RVM in normal animals. In rats treated with carrageenan, intra-CeA (S)-3,4-DCPG perfusion produced antinociception, and increased 5-HT and Glu, whereas it decreased GABA release. Intra-CeA (S)-3,4-DCPG inhibited ON and increased OFF cell activities. Furthermore, an increase in mGluR8 gene, protein, and staining, the latter being associated with vesicular GABA transporter-positive profiles, has been found in the CeA after carrageenan-induced inflammatory pain. These results show that stimulation of mGluR8, which was overexpressed within the CeA in inflammatory pain conditions, inhibits nociceptive behavior. Such an effect is associated with an increase in 5-HT and Glu release, a decrease in GABA, and the inhibition of ON-and the stimulation of OFF-cell activities within RVM.

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“…L-SOP might lower pain threshold by activating mGlu 7 receptors in the PAG. Accordingly, we have found that intra-PAG injection of the selective mGlu 7 receptor agonist, AMN082, produces a dose-dependent hyperalgesic effect, as monitored by behavioural [59] and in vivo electrophysiological studies (manuscript in preparation). Thus, mGlu 7 and mGlu 8 receptors may subserve opposite function within the PAG, producing hyperalgesic and analgesic effects, respectively.…”

Section: Periaqueductal Grey Metabotropic Glu-tamate Receptors In Paimentioning

confidence: 99%

“…We therefore examined the effect of the (S)-3,4-DCPG in models of inflammatory and neuropathic pain [59]. Systemic administration of (S)-3,4-DCPG decreased nociceptive responses in the formalin test.…”

Section: Periaqueductal Grey Metabotropic Glu-tamate Receptors In Paimentioning

confidence: 99%

Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing

Palazzos

Novellis²,

Marabese³

et al. 2006

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Metabotropic glutamate (mGlu) and cannabinoid receptors are G-protein coupled receptors which have shown synaptic co-operation through small lipid messengers in the central nervous system (CNS). A functional interaction between these two receptor families could have a relevant potential in the treatment of CNS disorders, including chronic pain. Indeed, both mGlu and cannabinoid receptors play a crucial role in the neurobiology of pain and their simultaneous manipulation could lead to novel strategies in pain management. In particular, as both mGlu and cannabinoid receptors have been found in the periaqueductal gray (PAG), a crucial station in the pain modulatory system, these receptors could be a substrate for producing analgesia at this level. In this review we aim to briefly illustrate the role of mGlu and cannabinoid receptors in controlling nociceptive processes, some points of convergence, and their functional interaction in pain processing. Further insights into this functional linkage between the mGlu and cannabinoid receptors could pave the way to a new strategy for pain relief, such as a drug cocktail acting on cannabinoid/metabotropic glutamate receptors.Key Words: Periaqueductal grey, metabotropic glutamate receptors; cannabinoid receptors, pain. METABOTROPIC GLUTAMATE RECEPTORS AND PAINMetabotropic glutamate (mGlu) receptors play an important role in the modulation of nociceptive processing and central sensitisation associated with persistent and chronic pain at several levels in the CNS [29,42,67,68].Several studies have shown that mGlu receptors modulate nociception from peripheral terminals [5,10,67,98,104]. This may stimulate the search for peripherally active mGlu receptor ligands, which are devoid of central adverse effects [30]. A role for mGlu receptors in spinal nociceptive processing has been reported, with particular emphasis on group I mGlu receptors [13,20,69,70,100,101,102,103]. Stimulation of group I mGlu receptors at spinal level generally produces pro-nociceptive effects [31,100], although functional differences between mGlu 1 and mGlu 5 receptors in modulating pain are recently emerging at the same rate as new selective mGlu receptor ligands are developed [69,90,101]. Spinal group I mGlu receptors also play an important role in nociceptive hypersensitivity associated with inflammation [8,69,101]. Intrathecal application of group II and group III agonists inhibit nociceptive responses [20,70,91], which may reflect the inhibition of glutamate release from nerve endings. Upregulation of mGlu 3 mRNA in the spinal cord following hind paw inflammation has also been reported [6]. A role for supraspinal mGlu receptors in the modulation of pain is also emerging, mGlu receptors modulate nociceptive responses at the level of ventrobasal thalamus [83][84][85], dorsal raphe [72] and amygdala [32,33,48]. This review will *Address correspondence to these authors at Department of Experimental Medicine, Section of Pharmacology "L. Donatelli"-Faculty of Medicine and Surgery, Second Universi...

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Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice

Cited by 56 publications

References 35 publications

Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082

Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082

Metabotropic Glutamate Receptor Subtype 8 in the Amygdala Modulates Thermal Threshold, Neurotransmitter Release, and Rostral Ventromedial Medulla Cell Activity in Inflammatory Pain

Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing

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