Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline

Asseri, Khalid A.; Puil, E.; Schwarz, Stephan; MacLeod, Bernard A.

doi:10.1016/j.neuroscience.2015.02.022

Cited by 10 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As repeated dosing with group II mGlu receptor agonists causes analgesic tolerance in rodents ( Jones et al, 2005 ; Chiechio et al, 2009 ), alternative strategies to reinforce endogenous activation of mGluR2 may be required to effectively target group II mGlu receptors for clinical pain relief. Our results suggest that recently developed mGluR2-specific positive allosteric modulators may be promising agents for blockade of peripheral sensitization ( Galici et al, 2006 ; Asseri et al, 2015 ).…”

Section: Discussionmentioning

confidence: 75%

“…The group II metabotropic glutamate receptors (mGluRs) have recently been identified as putative targets for pain relief in rodents ( Sharpe et al, 2002 ; Simmons et al, 2002 ; Yang and Gereau, 2002, 2003 ; Jones et al, 2005 ; Du et al, 2008 ; Osikowicz et al, 2008 ; Carlton et al, 2009, 2011 ; Zammataro et al, 2011 ; Asseri et al, 2015 ; Kolber, 2015 ; Chiechio, 2016 ; Johnson et al, 2017 ). mGluR2 and mGluR3 are seven transmembrane domain G i -protein coupled receptors that decrease cAMP formation, activate potassium channels, and inhibit voltage-gated calcium channels to reduce neuronal excitability and synaptic transmission ( Conn and Pin, 1997 ; Johnson and Schoepp, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although group II mGluRs are expressed at each level of the pain neuraxis ( Petralia et al, 1996 ; Tang and Sim, 1999 ; Carlton et al, 2001 ; Varney and Gereau, 2002 ; Carlton and Hargett, 2007 ; Boye Larsen et al, 2014 ; Kolber, 2015 ; Chiechio, 2016 ; Davidson et al, 2016 ), several lines of evidence suggest that activation of mGlu2 and mGlu3 receptors in peripheral sensory neurons is sufficient for analgesia. For instance, in rodent inflammatory pain models, pharmacological activation of mGluR2/3 expressed on peripheral primary afferents can attenuate pain-like behavior by suppressing sensory neuron sensitization in response to algogens and inflammatory mediators ( Yang and Gereau, 2002 ; Du et al, 2008 ; Carlton et al, 2011, 2009 ; Asseri et al, 2015 ; Davidson et al, 2016 ). Conversely, pharmacological inhibition of peripheral mGluR2/3 can prolong pain-like behavior and increase sensory neuron activity, suggesting that endogenous activation of mGluR2/3 is analgesic ( Yang and Gereau, 2003 ; Carlton et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabotropic Glutamate Receptor 2/3 (mGluR2/3) Activation Suppresses TRPV1 Sensitization in Mouse, But Not Human, Sensory Neurons

Sheahan¹,

Valtcheva²,

McIlvried³

et al. 2018

eNeuro

View full text Add to dashboard Cite

The use of human tissue to validate putative analgesic targets identified in rodents is a promising strategy for improving the historically poor translational record of preclinical pain research. We recently demonstrated that in mouse and human sensory neurons, agonists for metabotropic glutamate receptors 2 and 3 (mGluR2/3) reduce membrane hyperexcitability produced by the inflammatory mediator prostaglandin E2 (PGE2). Previous rodent studies indicate that mGluR2/3 can also reduce peripheral sensitization by suppressing inflammation-induced sensitization of TRPV1. Whether this observation similarly translates to human sensory neurons has not yet been tested. We found that activation of mGluR2/3 with the agonist APDC suppressed PGE2-induced sensitization of TRPV1 in mouse, but not human, sensory neurons. We also evaluated sensory neuron expression of the gene transcripts for mGluR2 (Grm2), mGluR3 (Grm3), and TRPV1 (Trpv1). The majority of Trpv1 + mouse and human sensory neurons expressed Grm2 and/or Grm3, and in both mice and humans, Grm2 was expressed in a greater percentage of sensory neurons than Grm3. Although we demonstrated a functional difference in the modulation of TRPV1 sensitization by mGluR2/3 activation between mouse and human, there were no species differences in the gene transcript colocalization of mGluR2 or mGluR3 with TRPV1 that might explain this functional difference. Taken together with our previous work, these results suggest that mGluR2/3 activation suppresses only some aspects of human sensory neuron sensitization caused by PGE2. These differences have implications for potential healthy human voluntary studies or clinical trials evaluating the analgesic efficacy of mGluR2/3 agonists or positive allosteric modulators.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabotropic Glutamate Receptor 2/3 (mGluR2/3) Activation Suppresses TRPV1 Sensitization in Mouse, But Not Human, Sensory Neurons

Sheahan¹,

Valtcheva²,

McIlvried³

et al. 2018

eNeuro

View full text Add to dashboard Cite

show abstract

“…Isovaline, an amino acid with analgesic properties, acts at a number of receptor types, including glycine receptors [95, 96]. MacLeod et al [95] experimented with isovaline to inhibit strychnine-induced pain in mice.…”

Section: How Do Pharmacological Interventions Take Advantage Of Pamentioning

confidence: 99%

“…Intravenous and intrathecal administration of isovaline showed promising analgesic effects; notably, without considerable systemic toxicity [95]. Asseri et al [96] demonstrated similar results, again without considerable CNS toxicity. Researchers have also used rats to study the anti-nociceptive effects of gelsemine, a plant-derived alkaloid with a mechanism similar to isovaline [97, 98].…”

Section: How Do Pharmacological Interventions Take Advantage Of Pamentioning

confidence: 99%

Transmission pathways and mediators as the basis for clinical pharmacology of pain

Kirkpatrick

McEntire

Smith

et al. 2016

Expert Review of Clinical Pharmacology

View full text Add to dashboard Cite

Introduction Mediators in pain transmission are the targets of a multitude of different analgesic pharmaceuticals. This review explores the most significant mediators of pain transmission as well as the pharmaceuticals that act on them. Areas Covered The review explores many of the key mediators of pain transmission. In doing so, this review uncovers important areas for further research. It also highlights agents with potential for producing novel analgesics, probes important interactions between pain transmission pathways that could contribute to synergistic analgesia, and emphasizes transmission factors that participate in transforming acute injury into chronic pain. Expert Commentary This review examines current pain research, particularly in the context of identifying novel analgesics, highlighting interactions between analgesic transmission pathways, and discussing factors that may contribute to the development of chronic pain after an acute injury.

show abstract

Antinociception by intrathecal delivery of the novel non‐opioid 1‐amino‐1‐cyclobutanecarboxylic acid

Fung

Asiri

Taheri³

et al. 2018

European Journal of Pain

View full text Add to dashboard Cite

show abstract

Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline

Cited by 10 publications

References 29 publications

Metabotropic Glutamate Receptor 2/3 (mGluR2/3) Activation Suppresses TRPV1 Sensitization in Mouse, But Not Human, Sensory Neurons

Metabotropic Glutamate Receptor 2/3 (mGluR2/3) Activation Suppresses TRPV1 Sensitization in Mouse, But Not Human, Sensory Neurons

Transmission pathways and mediators as the basis for clinical pharmacology of pain

Antinociception by intrathecal delivery of the novel non‐opioid 1‐amino‐1‐cyclobutanecarboxylic acid

Contact Info

Product

Resources

About