Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn.
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.
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- gamma-Aminobutyric Acid
- Synaptic Transmission
- Synapses
- Sciatic Neuropathy
- Receptors, N-Methyl-D-Aspartate
- Receptors, GABA-A
- Rats, Sprague-Dawley
- Rats
- Posterior Horn Cells
- Peripheral Nervous System Diseases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- gamma-Aminobutyric Acid
- Synaptic Transmission
- Synapses
- Sciatic Neuropathy
- Receptors, N-Methyl-D-Aspartate
- Receptors, GABA-A
- Rats, Sprague-Dawley
- Rats
- Posterior Horn Cells
- Peripheral Nervous System Diseases