Objective: Topiramate is an antiepileptic drug used also for the prophylaxis of migraine. It is known to inhibit voltage-gated sodium channels and to facilitate GABAergic action. The hemisected rodent cranial preparation is used to study the conduction properties of meningeal afferents, which are believed to be crucially involved in the generation of headaches. The effects of topiramate on the conduction of meningeal afferents were examined. Methods: The skull of adult rats was divided in the sagittal plane and the brain was removed leaving the cranial dura mater intact. A glass electrode was attached to spinosus nerve, the main nerve of the dura mater, after it was mobilised near the trigeminal ganglion. Action potentials of C-fibre afferents with receptive fields in the dura mater were recorded. The conduction velocity was monitored during electrical pulses at 2-4 Hz, which causes activity-dependent slowing. Increasing concentrations (10-100 mM) of topiramate and GABA were superfused during the stimulation protocol. A mechanical low-frequent stimulation protocol was run to evaluate the mechanical treshold during increasing concentrations of topiramate. Results: Topiramate did not cause significant changes in basal conduction velocity and in activity-dependent slowing. However, at 50 and 100 mM up to 68% of the nerve fibers underwent conduction failure in the course of the stimulation protocol. In contrast, during mechanical stimulation at low frequency (0.5 Hz), topiramate did not cause conduction failure and no change in mechanical threshold was seen. GABA had no influence on any conduction property but like topiramate it increased the electrical activation threshold. Conclusion: Topiramate can block nerve fibre conduction preferentially when fibers are activated, while the conduction velocity and the activity-dependent slowing, which has been found to be due to a long inactivation of sodium channels, is not influenced. The effect of topiramate could not be mimicked by GABA. This discrepancy may be explained by a multiple impact of topiramate.