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Papers of the Week

Papers: 18 Jul 2020 - 24 Jul 2020

Human Studies


2020 Jul 09


Identifying oxidized lipid mediators as prognostic biomarkers of chronic post-traumatic headache.


Domenichiello AF, Jensen JR, Zamora D, Horowitz M, Yuan Z-X, Faurot K, Mann DJ, Mannes AJ, Ramsden CE
Pain. 2020 Jul 09.
PMID: 32694380.


Chronic Post Traumatic Headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic non-traumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of the present study was to investigate whether circulating oxylipins measured in the acute setting following TBI, could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days post-injury with a neurobehavioral symptom inventory (NSI) and satisfaction with-life-survey (SWLS). Liquid chromatography tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosaheaxaenoic acid (DHA), and n-6 arachidonic acid (AA) and linoleic acid (LA).Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or SWLS scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (an LA derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.