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Phospholipase C activity increases in cerebrospinal fluid from migraineurs in proportion to the number of comorbid conditions: a case–control study

Alfred N Fonteh1*, Janice M Pogoda2, Rainbow Chung14, Robert P Cowan3 and Michael G Harrington1*

Author Affiliations

1 Molecular Neurology Program, Huntington Medical Research Institutes, 99 N El Molino Ave, Pasadena, CA 91101, USA

2 Statology, 158 W Cooke Rd, Columbus, OH 43214, USA

3 Department of Neurology, Stanford University School of Medicine, Stanford, CA 94305, USA

4 University of California, Irvine School of Medicine, Irvine, CA 92697, USA

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The Journal of Headache and Pain 2013, 14:60  doi:10.1186/1129-2377-14-60

Published: 4 July 2013



Migraineurs are more often afflicted by comorbid conditions than those without primary headache disorders, though the linking pathophysiological mechanism(s) is not known. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) activity in cerebrospinal fluid (CSF) increased during migraine compared to the same individual’s well state. Here, we examined whether PC-PLC activity from a larger group of well-state migraineurs is related to the number of their migraine comorbidities.


In a case–control study, migraineurs were diagnosed using International Headache Society criteria, and controls had no primary headache disorder or family history of migraine. Medication use, migraine frequency, and physician-diagnosed comorbidities were recorded for all participants. Lumbar CSF was collected between the hours of 1 and 5 pm, examined immediately for cells and total protein, and stored at −80°C. PC-PLC activity in thawed CSF was measured using a fluorometric enzyme assay. Multivariable logistic regression was used to evaluate age, gender, medication use, migraine frequency, personality scores, and comorbidities as potential predictors of PC-PLC activity in CSF.


A total of 18 migraineurs-without-aura and 17 controls participated. In a multivariable analysis, only the number of comorbidities was related to PC-PLC activity in CSF, and only in migraineurs [parameter estimate (standard error) = 1.77, p = 0.009].


PC-PLC activity in CSF increases with increasing number of comorbidities in migraine-without-aura. These data support involvement of a common lipid signaling pathway in migraine and in the comorbid conditions.

CSF; PLC; Depression; Irritable bowel syndrome; Painful bladder