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Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat

The metabotropic glutamate receptor 7 (mGluR7) negative allosteric modulator, 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), was locally microinjected into the ventrolateral periaqueductal gray (VL PAG) and the effect on pain responses in formalin and spare ner...

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Autores principales: Palazzo, Enza, Marabese, Ida, Luongo, Livio, Boccella, Serena, Bellini, Giulia, Giordano, Maria Elvira, Rossi, Francesca, Scafuro, Mariantonietta, Novellis, Vito de, Maione, Sabatino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846361/
https://www.ncbi.nlm.nih.gov/pubmed/24004843
http://dx.doi.org/10.1186/1744-8069-9-44
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author Palazzo, Enza
Marabese, Ida
Luongo, Livio
Boccella, Serena
Bellini, Giulia
Giordano, Maria Elvira
Rossi, Francesca
Scafuro, Mariantonietta
Novellis, Vito de
Maione, Sabatino
author_facet Palazzo, Enza
Marabese, Ida
Luongo, Livio
Boccella, Serena
Bellini, Giulia
Giordano, Maria Elvira
Rossi, Francesca
Scafuro, Mariantonietta
Novellis, Vito de
Maione, Sabatino
author_sort Palazzo, Enza
collection PubMed
description The metabotropic glutamate receptor 7 (mGluR7) negative allosteric modulator, 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), was locally microinjected into the ventrolateral periaqueductal gray (VL PAG) and the effect on pain responses in formalin and spare nerve injury (SNI) -induced neuropathic pain models was monitored in the rat. The activity of rostral ventromedial medulla (RVM) “pronociceptive” ON and “antinociceptive” OFF cells was also evaluated. Intra–VL PAG MMPIP blocked the first and second phase of nocifensive behaviour in the formalin pain model. MMPIP increased the tail flick latency and simultaneously increased the activity of the OFF cells while inhibiting that of ON cells in rats with SNI of the sciatic nerve. MMPIP failed to modify nociceptive responses and associated RVM ON and OFF cell activity in sham rats. An increase in mGluR7 gene, protein and staining, the latter being associated with vesicular glutamate transporter-positive profiles, has been found in the VL PAG in SNI rats. Blockade of mGluR7 within the VL PAG has an antinociceptive effect in formalin and neuropathic pain models. VL PAG mGluR7 blockade offers a target for dis-inhibiting the VL PAG-RVM pathway and silencing pain in inflammatory and neuropathic pain models.
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spelling pubmed-38463612013-12-03 Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat Palazzo, Enza Marabese, Ida Luongo, Livio Boccella, Serena Bellini, Giulia Giordano, Maria Elvira Rossi, Francesca Scafuro, Mariantonietta Novellis, Vito de Maione, Sabatino Mol Pain Research The metabotropic glutamate receptor 7 (mGluR7) negative allosteric modulator, 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), was locally microinjected into the ventrolateral periaqueductal gray (VL PAG) and the effect on pain responses in formalin and spare nerve injury (SNI) -induced neuropathic pain models was monitored in the rat. The activity of rostral ventromedial medulla (RVM) “pronociceptive” ON and “antinociceptive” OFF cells was also evaluated. Intra–VL PAG MMPIP blocked the first and second phase of nocifensive behaviour in the formalin pain model. MMPIP increased the tail flick latency and simultaneously increased the activity of the OFF cells while inhibiting that of ON cells in rats with SNI of the sciatic nerve. MMPIP failed to modify nociceptive responses and associated RVM ON and OFF cell activity in sham rats. An increase in mGluR7 gene, protein and staining, the latter being associated with vesicular glutamate transporter-positive profiles, has been found in the VL PAG in SNI rats. Blockade of mGluR7 within the VL PAG has an antinociceptive effect in formalin and neuropathic pain models. VL PAG mGluR7 blockade offers a target for dis-inhibiting the VL PAG-RVM pathway and silencing pain in inflammatory and neuropathic pain models. BioMed Central 2013-09-03 /pmc/articles/PMC3846361/ /pubmed/24004843 http://dx.doi.org/10.1186/1744-8069-9-44 Text en Copyright © 2013 Palazzo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Palazzo, Enza
Marabese, Ida
Luongo, Livio
Boccella, Serena
Bellini, Giulia
Giordano, Maria Elvira
Rossi, Francesca
Scafuro, Mariantonietta
Novellis, Vito de
Maione, Sabatino
Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title_full Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title_fullStr Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title_full_unstemmed Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title_short Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
title_sort effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846361/
https://www.ncbi.nlm.nih.gov/pubmed/24004843
http://dx.doi.org/10.1186/1744-8069-9-44
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