Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn

Mol Cell Neurosci. 2003 Nov;24(3):818-30. doi: 10.1016/s1044-7431(03)00236-7.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Denervation / adverse effects
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Fibers, Myelinated / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / physiopathology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Posterior Horn Cells / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sciatic Neuropathy / metabolism
  • Sciatic Neuropathy / physiopathology
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*


  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • GABA Antagonists
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid
  • Mitogen-Activated Protein Kinases