The aim of this study was to investigate the efficacy of riboflavin for the prevention of migraine. An open label study was performed in a specialized outpatient clinic. Patients received 400 mg riboflavin capsules per day. Headache frequency, duration, intensity and the use of abortive drugs were recorded at baseline and 3 and 6 months after treatment. Headache frequency was significantly reduced from 4 days/month at baseline to 2 days/month after 3 and 6 months (P < 0.05). The use of abortive drugs decreased from 7 units/month to 4.5 units/month after 3 and 6 months of treatment (P < 0.05). In contrast, headache hours and headache intensity did not change significantly. We could demonstrate a significant reduction of headache frequency following riboflavin treatment. In addition, the number of abortive anti-migraine tablets was reduced. In line with previous studies our findings show that riboflavin is a safe and well-tolerated alternative in migraine prophylaxis.

ObjectivePro-inflammatory cytokines like Interleukin-1 beta (IL-1β) have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP) are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX) inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified.Methods and Results1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE2) release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib) and a non-selective COX-inhibitor (indomethacin). 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE2 and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect.ConclusionWe identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE2 (by COX-2) in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2 and CGRP. The results could help to explain the mechanism of action of COX-2 inhibitors in migraine.

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