Abstract
Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the initial, fast response. A-fiber-induced ERK activation is also facilitated in the presence of bicuculline. The frequency of miniature EPSCs and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A) receptors located on somatodendritic sites of excitatory interneurons are critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented ERK activation. This NMDA receptor-dependent phenomenon may contribute to bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity observed in neuropathic pain patients.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Denervation / adverse effects
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Disease Models, Animal
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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GABA Agonists / pharmacology
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GABA Antagonists / pharmacology
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Male
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Mitogen-Activated Protein Kinases / metabolism
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Nerve Fibers, Myelinated / physiology*
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neuralgia / metabolism*
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Neuralgia / physiopathology
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Peripheral Nervous System Diseases / metabolism
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Peripheral Nervous System Diseases / physiopathology
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Posterior Horn Cells / drug effects
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Posterior Horn Cells / metabolism*
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Posterior Horn Cells / physiopathology
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Rats
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Rats, Sprague-Dawley
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Receptors, GABA-A / drug effects
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Receptors, GABA-A / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism
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Sciatic Neuropathy / metabolism
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Sciatic Neuropathy / physiopathology
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Synapses / drug effects
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Synapses / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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gamma-Aminobutyric Acid / metabolism*
Substances
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Excitatory Amino Acid Antagonists
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GABA Agonists
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GABA Antagonists
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Receptors, GABA-A
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Receptors, N-Methyl-D-Aspartate
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gamma-Aminobutyric Acid
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Mitogen-Activated Protein Kinases