SPINAL BICUCULLINE PRODUCES HYPERSENSITIVITY OF DORSAL HORN NEURONS -EFFECTS OF EXCITATORY AMINO-ACID ANTAGONISTS

In this study, we sought to characterize the effects of focal GABAA re ceptor antagonism on spontaneous and evoked activity in dorsal horn ne urons of the cr-chloralose anesthetized cat. Bicuculline (0.5, 1.0 mM) applied near the neurons through a transparenchymal dialysis fiber re sulted in increased evoked activity in nociceptive dorsal horn neurons . Hair deflection was the stimulus most affected, followed by both low and high threshold tonic mechanical stimulation of the receptive fiel d. In addition, neurons displayed increased background discharge and a subpopulation developed an increased afterdischarge to noxious mechan ical stimulation. This is in contrast to our previous work with glycin e receptor antagonism where only the evoked response to hair follicle activation was significantly enhanced. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) was without any apparent e ffect on either basal or bicuculline enhanced responses. Go-administra tion of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1. 0 mM) with the bicuculline non-selectively blocked both low and high t hreshold mechanical input. The inability of AP-7 to reverse the bicucu lline-associated hyperreactivity also contrasts with the AP-7 reversal of the strychnine-associated hyperreactivity. These results point out that, while GABA and glycine are frequently co-localized in cells of the spinal dorsal horn and both appear to mediate tonic inhibitory con trol systems, they are not at all equivalent and are subject to differ ent modulatory pharmacologies. Removal of each influence may model a d ifferent component of neuropathic pain. (C) 1998 International Associa tion for the Study of Pain. Published by Elsevier Science B.V.