Can Metabotropic Glutamate Receptor 7 (mGluR 7) be a Novel Target for Analgesia?

Suvarna, Punya; Hadigal, Sanjay; Kamath, Padmanabh; Prabhu, Nayana; Shenoy, Nandita; Prasanna, LC

doi:10.7860/jcdr/2014/10377.4884

Cited by 5 publications

(3 citation statements)

References 14 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMN082 has also been shown to decrease responses in a model of cardiac nociception ( Liu et al., 2012 ). However, conflicting evidence has also emerged showing that AMN082 induces a hyperalgesic response in both the hotplate and tail flick assays ( G et al, 2014 )…”

Section: Discussionmentioning

confidence: 99%

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

Moloney

Golubeva

O’Connor

et al. 2015

Neurobiology of Stress

View full text Add to dashboard Cite

Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

show abstract

Section: Discussionmentioning

confidence: 99%

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

Moloney

Golubeva

O’Connor

et al. 2015

Neurobiology of Stress

View full text Add to dashboard Cite

show abstract

“…An mGluR7 PAM (AMN082, i.p.) had no effect in the hot plate and tail flick tests in rats under normal conditions [ 153 ] but blocked thermal hyperalgesia and mechanical allodynia in the carrageenan inflammatory model and had beneficial effects on the thermal, but not mechanical, responses in the hindpaw incision model [ 154 ]. AMN082 (i.p.)…”

Section: Group III Mglurs In Preclinical Pain Modelsmentioning

confidence: 99%

Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors

Mazzitelli

Presto

Antenucci

et al. 2022

Cells

View full text Add to dashboard Cite

Metabotropic glutamate receptors (mGluR or mGlu) are G-protein coupled receptors activated by the binding of glutamate, the main classical neurotransmitter of the nervous system. Eight different mGluR subtypes (mGluR1-8) have been cloned and are classified in three groups based on their molecular, pharmacological and signaling properties. mGluRs mediate several physiological functions such as neuronal excitability and synaptic plasticity, but they have also been implicated in numerous pathological conditions including pain. The availability of new and more selective allosteric modulators together with the canonical orthosteric ligands and transgenic technologies has led to significant advances in our knowledge about the role of the specific mGluR subtypes in the pathophysiological mechanisms of various diseases. Although development of successful compounds acting on mGluRs for clinical use has been scarce, the subtype-specific-pharmacological manipulation might be a compelling approach for the treatment of several disorders in humans, including pain; this review aims to summarize and update on preclinical evidence for the roles of different mGluRs in the pain system and discusses knowledge gaps regarding mGluR-related sex differences and neuroimmune signaling in pain.

show abstract

“…1. The systemic administration of AMN082 has shown to both, facilitate [162] or inhibit pain responses [163]. Moreover, AMN082 potentiated the analgesic effect of morphine or glial inhibitors [163,164].…”

Section: Mglur7 and Painmentioning

confidence: 99%

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

Boccella

Marabese

Guida

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Can Metabotropic Glutamate Receptor 7 (mGluR 7) be a Novel Target for Analgesia?

Cited by 5 publications

References 14 publications

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors

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

Contact Info

Product

Resources

About