Original article. Potential risk of dihydroergotamine causing medicationoveruse headache: preclinical evidence

Background: Overuse of abortive medication is a common factor contributing to an increase in headache frequency in patients with migraine. Whether or not chronic exposure to dihydroergotamine (DHE) can lead to this transformation remains uncertain.

Objective: To determine the effect of acute and chronic DHE exposure on development of cortical spreading depression (CSD) and trigeminal nociception.

Methods: The study comprised two experiments, namely acute and chronic exposure. In the acute experiment, a single dose of DHE (100 μg/kg) was given to male Wistar rats after successful induction of CSD. In the chronic experiment, DHE was given daily for the period of 0, 7, 14, and 28 days. CSD was induced 30 minutes after the final injection and the cortical field potential was recorded. Expression of c-Fos in caudal brainstem was used as an indicator of trigeminal nociception.

Results: Acute exposure to DHE attenuated the expression of c-Fos in the caudal brainstem without change in CSD response. By contrast, chronic exposure (14 and 28 days) to DHE increased the area under the curve of CSD waveforms. In parallel with the change in the CSD, there was significant increase of c-Fos expression within 14 days exposure to DHE and the expression remained significantly elevated for up to the 28 days examined.

Conclusion: Our study demonstrated that chronic DHE administration can increase cortical excitability and increase c-Fos expression in caudal brainstem. Our preclinical evidence suggests the possible adverse effect of chronic DHE use in causing chronification of headache.