The long-term objective of our research is to discover what clinical and molecular changes occur before, during and after severe headaches. Our hypothesis is that the myriad headache triggers and behavioral expressions are mediated through interacting molecular pathways that may be studied by temporal, compositional analysis of accessible body fluids, in particular cerebrospinal fluid (CSF). Preliminary results have revealed many ictal changes in proteins, lipids and elements that reflect these migraine 'gateway' pathways, the magnitude of which reflect the clinical severity of the migraine ictus, suggesting a corresponding 'molecular ictus'. We propose to further dissect this clinical and molecular ictus by the analysis of CSF from migraineurs in headache and non-headache states, episodic tension headache sufferers and 'controls' who do not suffer from headaches. We will test the role of protein, lipid and elemental changes in headache by defining their molecular composition by 2D gel electrophoresis, liquid chromatography and mass spectrometry in temporally spaced collections from clinically well defined participants. Delineation of these compositional differences should extend our pathophysiological understanding beyond the current theories, yield useful biomarkers and lead to more knowledge-based remedies or interventions.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Porter, Linda L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Huntington Medical Research Institutes
United States
Zip Code
Fonteh, Alfred N; Pogoda, Janice M; Chung, Rainbow et al. (2013) Phospholipase C activity increases in cerebrospinal fluid from migraineurs in proportion to the number of comorbid conditions: a case-control study. J Headache Pain 14:60
Fonteh, Alfred N; Chung, Rainbow; Sharma, Tara L et al. (2011) Cerebrospinal fluid phospholipase C activity increases in migraine. Cephalalgia 31:456-62
Arakaki, Xianghong; Foster, Hailey; Su, Lei et al. (2011) Extracellular sodium modulates the excitability of cultured hippocampal pyramidal cells. Brain Res 1401:85-94
Harrington, Michael G; Chekmenev, Eduard Y; Schepkin, Victor et al. (2011) Sodium MRI in a rat migraine model and a NEURON simulation study support a role for sodium in migraine. Cephalalgia 31:1254-65
Harrington, Michael G; Salomon, Ronald M; Pogoda, Janice M et al. (2010) Cerebrospinal fluid sodium rhythms. Cerebrospinal Fluid Res 7:3
Fonteh, Alfred N; Fisher, Rachel D (2009) Combining lipidomics and proteomics of human cerebrospinal fluids. Methods Mol Biol 579:71-86
Fonteh, A N; Harrington, R J; Tsai, A et al. (2007) Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids 32:213-24
Fonteh, A N; Harrington, R J; Harrington, M G (2007) Quantification of free amino acids and dipeptides using isotope dilution liquid chromatography and electrospray ionization tandem mass spectrometry. Amino Acids 32:203-12
Harrington, Michael G; Fonteh, Alfred N; Cowan, Robert P et al. (2006) Cerebrospinal fluid sodium increases in migraine. Headache 46:1128-35