Abstract
BackgroundMigraineurs 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.MethodsIn 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.ResultsA 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].ConclusionPC-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.
Highlights
Migraineurs are more often afflicted by comorbid conditions than those without primary headache disorders, though the linking pathophysiological mechanism(s) is not known
cerebrospinal fluid (CSF) cell counts and total proteins were within normal ranges in both controls and migraineurs
Higher PC-Phospholipase C (PLC) activity in migraineurs compared to controls, the sex difference we observed is consistent with the higher incidence of migraine in the female population
Summary
Migraineurs are more often afflicted by comorbid conditions than those without primary headache disorders, though the linking pathophysiological mechanism(s) is not known. We examined whether PC-PLC activity from a larger group of well-state migraineurs is related to the number of their migraine comorbidities. Depression, the most common comorbid condition, and migraine are among the highest ranked causes of global years lived with disability [2]. To consider common biochemical pathways, migraine and many of its comorbidities have been found to share alterations in serotonin [16], noradrenaline [17,18], estrogen [19], cannabinoids [20,21], and glutamate [22,23]. Since the signaling pathways for these ligand-bound GPCRs involve PC-PLC activation [26,27,28], we hypothesize that migraine and its comorbidities share a common pathway of receptormediated, lipid second-messengers that are regulated by PLC activation. Newly identified peptides such as orexin and ghrelin, which are known to regulate sleep-wakefulness, mediate their excitatory effects on the pedunculopontine tegmental nucleus by PLC activation [31]
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