Introduction: Research in migraine therapeutics is hindered by the lack of knowledge on migraine pathophysiology and suitable predictive animal models. As headache and migraine can be provoked in healthy humans and migraine patients the aim of this study was to see if it can also provoke headache in rats. Also, we tested the response to sumatriptan in order to evaluate the predictive properties of the model.

Methods: The effect of cilostazol (125 mg/kg p.o.) was evaluated on a range of spontaneous behavioural parameters, light sensitivity and mechanical sensitivity thresholds. To assess headache specificity we evaluated the c-fos expression in the trigeminal nucleus caudalis. All experiments were done in female Sprague Dawley rats and the oestrous cycle was included in the analyses.

Results: We found that cilostazol increased the light sensitivity and grooming behaviour of the rats and decreased their head twitching. These manifestations were not inhibited by sumatriptan. Cilostazol also induced c-fos expression in the trigeminal nucleus caudalis. Locomotion, rearing, eating and drinking activity as well as the amount of wet dog shakes and mechanical sensitivity thresholds were unaltered.

Discussion: The altered behaviours are suggestive of headache with migraine features, but not specific. The c-fos response in the trigeminal nucleus caudalis implies that the rats had pain originating from the head. The lack of response to sumatriptan disqualifies the model as predictive, but confirms the translation of the human findings into rats.