The purpose of this study was to investigate the allodynic effect of
bicuculline (
BIC) given topically to the dorsal surface of the rat spinal cord, and to determine if spinal
prostaglandins (PGs) mediate the allodynic state arising from spinal
GABA(A)-receptor blockade. Male Sprague-Dawley rats (325-400 g) were anaesthetized with
halothane and maintained with
urethane for the continuous monitoring of blood pressure (MAP), heart rate (HR) and cortical electroencephalogram (EEG). A
laminectomy was performed to expose the dorsal surface of the spinal cord. Unilateral application of
BIC (0.1 microg in 0.1 microl) to the L5 or L6 spinal segment induced a highly localized
allodynia (e.g. one or two digits) on the ipsilateral hind paw. Thus, hair deflection (brushing the hair with a cotton-tipped applicator) in the presence, but not absence of
BIC, evoked an increase in MAP and HR, abrupt motor responses (MR; e.g. withdrawal of the hind leg, kicking, and/or scratching) on the affected side, and desynchrony of the EEG.
BIC-
allodynia was dose-dependent, yielding ED(50)'s (95% CI's) of 45 ng (31-65) for MAP; 68 ng (46-101) for HR and 76 ng (60-97) for MR.
Allodynia was sustained for up to 2 h with repeated
BIC application without any detectable change in the location or area of peripheral sensitization. Pretreatment with either the EP(1)- receptor antagonist, SC-51322, the
cyclooxygenase (COX)-2 selective inhibitor,
NS-398, or the
NMDA-receptor antagonist,
AP-7, inhibited
BIC-
allodynia in a dose-dependent manner. The results demonstrate: (a)
BIC, applied to the dorsal surface of the spinal cord, induces highly localized
allodynia; (b) this effect can be sustained with repeated
BIC application; (c) it is evoked by
NMDA-dependent afferent input; (d) spinal PGs are synthesized by constitutive COX-2 during
BIC-
allodynia; and (e) spinal PGs contribute to the abnormal processing of tactile input via spinal EP1-receptors.