Presynaptic mGluR5 receptor controls glutamatergic input through protein kinase C-NMDA receptors in paclitaxel-induced neuropathic pain

The Journal of Biological Chemistry
Jing-Dun XieHui-Lin Pan

Abstract

Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root. DHPG also reduced the paired-pulse ratio of evoked EPSCs in spinal dorsal horn neurons. These effects were blocked by the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), but not by an mGluR1 antagonist. MPEP normalized the frequency of miniature EPSCs and the amplitude of evoked EPSCs in paclitaxel-treated rats but had no effect in vehicle-treated rats. Furthermore, mGluR5 protein levels in the dorsal root ganglion and spinal cord synaptosomes were significantly higher in paclitaxel- than in vehicle-treated rats. Inhibiting...Continue Reading

References

Jan 1, 1995·Neuropharmacology·J P Pin, R Duvoisin
Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·P J Conn, J P Pin
Aug 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·María Cecilia AnguloEtienne Audinat
Mar 3, 2007·The Journal of Physiology·Sónia F A SantosBoris V Safronov
Jul 6, 2007·The European Journal of Neuroscience·Claudia G WernerDomenico E Pellegrini-Giampietro
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hao Huang, Anthony N van den Pol
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Colleen M Niswender, P Jeffrey Conn
Mar 26, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hong-Yi ZhouHui-Lin Pan
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Jan 21, 2011·The Journal of Pharmacology and Experimental Therapeutics·Shao-Rui ChenHui-Lin Pan
Mar 22, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·De-Pei LiHui-Lin Pan
Jun 6, 2014·The Journal of Pharmacology and Experimental Therapeutics·Shao-Rui ChenHui-Lin Pan
Nov 5, 2014·Nature Reviews. Neurology·Marco SisignanoGerd Geisslinger

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Citations

Feb 23, 2019·Cellular and Molecular Life Sciences : CMLS·Meichun DengHui-Lin Pan
Apr 18, 2018·Current Neuropharmacology·David Agustín León-NavarroMairena Martín
Jun 5, 2020·Molecular Pain·Xiangyang MeiZhiying Feng
Jan 22, 2019·Frontiers in Molecular Neuroscience·Vanessa Pereira, Cyril Goudet
Dec 20, 2020·Clinical and Translational Science·Chenling XiongDeanna L Kroetz
Nov 4, 2020·The Journal of Physiology·Hovy Ho-Wai WongP Jesper Sjöström
Jul 28, 2021·Acta Oncologica·Cornelia J C VermeerNiels Eijkelkamp
Jan 6, 2019·ACS Chemical Neuroscience·R GanugulaM N V Ravi Kumar
Feb 3, 2022·ACS Chemical Neuroscience·Krishna Ghosh, Hui-Lin Pan

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