Mechanisms of bicuculline-induced hypersensitivity of medullary dorsal horn neurons in rats

The purpose of the present study was to examine the responses of medullary dorsal horn neurons to microiontophoretic application of the γ-aminobutyric acid (GABA)_A receptor antagonist, bicuculline. The mechanisms of bicuculline-induced hypersensitivity were also investigated. Extracellular recordings were made with the central barrel of a seven-barrel micropipette. Microiontophoretic application of bicuculline greatly increased N-methyl-D-aspartic acid (NMDA)-evoked responses of medullary dorsal horn neurons. Bicuculline also increased the responses to both noxious pinching and brushing of cutaneous receptor fields. Both NMDA and non-NMDA receptor antagonists blocked the facilitated responses to iontophoretic application of bicuculline. However, the mu and delta receptor agonists did not block the hypersensitivity produced by iontophoretic application of bicuculline. These results suggest that GABA modulates the synaptic transmission of both noxious and non-noxious information in the trigeminal spinal sensory nuclei. Bicuculline-induced hypersensitivity seems to be mediated by excitatory amino acid receptors and provides a mechanism for neuropathic pain.