MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice

Pain
Enza PalazzoSabatino Maione

Abstract

This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. Cognitive performance was also significantly compromised in the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons of the PLC; excitatory responses increased, whereas inhibitory responses decreased after BLA stimulation. mGluR7 expression, mainly associated with vesicular glutamate transporter, increased in the hippocampus and decreased in the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and mechanical thre...Continue Reading

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Citations

Jun 27, 2015·Neuropharmacology·Claudia SaghedduMarco Pistis
Jul 2, 2016·Journal of Neurochemistry·Enza PalazzoSabatino Maione
Nov 9, 2018·Frontiers in Molecular Neuroscience·Nicole M FisherColleen M Niswender
Feb 29, 2020·Pain·Alexandra PokhilkoM Zameel Cader
Jan 22, 2019·Frontiers in Molecular Neuroscience·Vanessa Pereira, Cyril Goudet
May 18, 2020·International Journal of Molecular Sciences·Kai K KummerMichaela Kress
May 15, 2020·International Journal of Molecular Sciences·Francesca GuidaSabatino Maione
Oct 9, 2018·Frontiers in Molecular Neuroscience·Paulina CieślikJoanna Wierońska
Jul 19, 2019·Neurochemical Research·Priscila MedeirosNorberto Cysne Coimbra
Feb 26, 2019·Frontiers in Molecular Neuroscience·Rosalia CrupiSalvatore Cuzzocrea
Jun 19, 2019·Current Neuropharmacology·Serena BoccellaEnza Palazzo
Jan 7, 2020·Behavioral and Brain Functions : BBF·Soonmi WonSung Joong Lee
Feb 15, 2021·Brain Structure & Function·James W M KangKevin A Keay
Mar 12, 2021·Science Translational Medicine·Ana M MorenoPrashant Mali
Sep 28, 2020·Neuroscience and Biobehavioral Reviews·Ana Margarida CunhaHugo Leite-Almeida
Apr 10, 2018·ACS Chemical Neuroscience·Takaki Kiritoshi, Volker Neugebauer

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