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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Baba, H; Ji, R-R; Kohno, T; Moore, KA; Ataka, T; Wakai, A; Okamoto, M; Woolf, CJ

Published Date

  • November 2003

Published In

Volume / Issue

  • 24 / 3

Start / End Page

  • 818 - 830

PubMed ID

  • 14664828

Pubmed Central ID

  • 14664828

Electronic International Standard Serial Number (EISSN)

  • 1095-9327

International Standard Serial Number (ISSN)

  • 1044-7431

Digital Object Identifier (DOI)

  • 10.1016/s1044-7431(03)00236-7

Language

  • eng