Abstract
The spinal synaptic plasticity is associated with a central sensitization of nociceptive input, which accounts for the generation of hyperalgesia in chronic pain. However, how group I metabotropic glutamate receptors (mGluRs) may operate spinal plasticity remains essentially unexplored. Here, we have identified spike-timing dependent synaptic plasticity in substantia gelatinosa (SG) neurons, using perforated patch-clamp recordings of SG neuron in a spinal cord slice preparation. In the presence of bicuculline and strychnine, long-term potentiation (LTP) was blocked by AP-5 and Ca2+ chelator BAPTA-AM. The group I mGluR antagonist AIDA, PLC inhibitor U-73122, and IP3 receptor blocker 2-APB shifted LTP to long-term depression (LTD) without affecting acute synaptic transmission. These findings provide a link between postsynaptic group I mGluR/PLC/IP3-gated Ca2+ store regulating the polarity of synaptic plasticity and spinal central sensitization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Boron Compounds / pharmacology
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Calcium / antagonists & inhibitors
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Calcium / metabolism
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Calcium Channels
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Chelating Agents / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Estrenes / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Female
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Indans / pharmacology
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Inositol 1,4,5-Trisphosphate Receptors
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Male
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Neurons / drug effects
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Neurons / physiology*
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Pyrrolidinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / physiology*
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Staurosporine / pharmacology
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Substantia Gelatinosa / cytology
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Substantia Gelatinosa / drug effects
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Substantia Gelatinosa / physiology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Time Factors
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Type C Phospholipases / antagonists & inhibitors
Substances
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1-aminoindan-1,5-dicarboxylic acid
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Boron Compounds
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Calcium Channels
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Chelating Agents
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Estrenes
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Excitatory Amino Acid Antagonists
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Indans
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Inositol 1,4,5-Trisphosphate Receptors
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Pyrrolidinones
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Receptors, Cytoplasmic and Nuclear
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor type 1
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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2-Amino-5-phosphonovalerate
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2-aminoethoxydiphenyl borate
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Type C Phospholipases
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Staurosporine
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Calcium