Cerebrospinal fluid phospholipase C activity increases in migraine

Cephalalgia. 2011 Mar;31(4):456-62. doi: 10.1177/0333102410383589. Epub 2010 Oct 11.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Bridged-Ring Compounds / pharmacology
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / blood
  • Migraine Disorders / cerebrospinal fluid*
  • Migraine Disorders / enzymology*
  • Norbornanes
  • Phosphatidylcholines / cerebrospinal fluid
  • Thiocarbamates
  • Thiones / pharmacology
  • Type C Phospholipases / blood
  • Type C Phospholipases / cerebrospinal fluid*


  • Biomarkers
  • Bridged-Ring Compounds
  • Norbornanes
  • Phosphatidylcholines
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Type C Phospholipases
  • phosphatidylcholine-specific phospholipase C