Associations Between Fatty Acid Levels in Human Blood and Trigeminovascular Tissues

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are precursors to oxylipins that modulate pain and inflammation. We previously demonstrated that (1) a dietary intervention increasing omega-3 and reducing omega-6 PUFAs alters the concentration of these oxylipin precursors in blood, and (2) these changes are associated with reduced headache pain in humans. However, the extent to which blood levels reflect trigeminovascular tissues remains unclear. We sought to determine whether oxylipin precursor PUFA levels in blood reflect those in the meninges, cranial arteries, and trigeminal ganglia. Precursor PUFA compositions of post-mortem blood and trigeminovascular tissue specimens from 70 individuals, procured from the Human Brain Collection Core at the National Institute of Mental Health, were quantified. Regression models adjusted for confounders examined relationships between blood and tissue PUFA levels. Eicosapentaenoic acid in blood was associated with levels in cranial arteries, meninges, and trigeminal ganglia [logged coefficients (p value): 0.29 (0.019); 0.37 (< 0.001); 0.25 (0.009)]. Other PUFAs, including linoleic acid, arachidonic acid, n-6 docosapentaenoic acid, and docosahexaenoic acid, also showed significant associations between blood and meninges and/or trigeminal ganglia levels. These findings support using blood measurements of certain PUFAs as a proxy for their concentration in tissues directly involved in headache pathogenesis.