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Cerebrospinal fluid phospholipase C activity increases in migraine

Background: Adrenaline, serotonin, cannabinoid and estrogen receptors are involved in migraine pathophysiology. The signaling of these receptors change phosphatidylcholine-specific phospholipase C (PC-PLC) activity, but there have been no reported PC-PLC studies in migraine. Methods: We identified PC-PLC activity in blood and cerebrospinal fluid (CSF), and quantified it in samples from ictal and interictal migraineurs without aura and healthy controls. Results: Pre-incubation with a specific PC-PLC inhibitor, D609, inhibited enzyme activity (p < .0001) and confirms its presence in CSF. PC-PLC activity was higher in the CSF from ictal migraineurs compared to controls (mean relative fluorescence unit [RFU]/µg/min [standard deviation, SD] 13.1 [3.07] vs. 9.3 [1.97]; p = .002) and, in a paired analysis, in migraineurs during ictal compared to interictal states (11.7 [1.6] vs. 7.9 [1.5]; p = .02). CSF PC-PLC activity in the ictal state correlated negatively with migraine frequency (r = −0.82). Plasma PC-PLC activity was 250–300 times less than in CSF and did not increase in migraine, implicating the brain as the source of the CSF enzyme changes. Conclusion: This is the first report of PC-PLC activity in CSF and of its alteration in migraine. We propose that these PC-PLC changes in CSF reflect the overall receptor fluctuations in migraine.