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Prior work showed that diet shifts in omega-3/omega-6 PUFAs change oxylipin precursor levels in blood and correspond to lower headache pain, but how well blood mirrors trigeminovascular tissues is uncertain. This study quantified PUFA precursor profiles in post-mortem blood and trigeminovascular specimens from 70 individuals and used regression models adjusted for confounders. Eicosapentaenoic acid in blood related to levels in cranial arteries, meninges, and trigeminal ganglia, and several other PUFAs also showed significant blood–tissue associations, supporting blood measures as a proxy for certain tissue concentrations involved in headache biology.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/associations-between-fatty-acid-levels-in-human-blood-and-trigeminovascular-tissues/458273/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/associations-between-fatty-acid-levels-in-human-blood-and-trigeminovascular-tissues/458273.png","ImageObject",300,407,{"name":92,"@type":93},"\tCallum ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What biological pathway links omega-3/omega-6 PUFAs to headache-related pain?","Question",{"text":112,"@type":113},"Omega-3 and omega-6 PUFAs are precursors to oxylipins that modulate pain and inflammation. The paper also discusses potential mechanisms involving trigeminal ganglia receptors and TRP channel–related signaling that can influence headache processes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study compare PUFA precursor levels between blood and trigeminovascular tissues?",{"text":117,"@type":113},"The study quantified precursor PUFA compositions in post-mortem blood and trigeminovascular tissue specimens from 70 individuals. Regression models adjusted for confounders assessed relationships between blood and tissue PUFA levels.",{"name":119,"@type":110,"acceptedAnswer":120},"Which blood fatty acid showed associations with trigeminovascular tissue levels?",{"text":121,"@type":113},"Eicosapentaenoic acid (EPA) in blood was associated with PUFA levels in cranial arteries, meninges, and trigeminal ganglia. Other listed PUFAs, including linoleic acid and arachidonic acid, also showed significant blood–tissue associations in meninges and/or trigeminal ganglia.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},458273,1790794851,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},137451211410,"https://ap-avatar.wpscdn.com/avatar/2000bb0a9246f588df?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786362646172706240","Lipids  \nORIGINAL ARTICLE  OPEN ACCESS   \nAssociations Between Fatty Acid Levels in Human Blood and Trigeminovascular Tissues  \nDaisy Zamora1,2 | Mark S. Horowitz1  | Sharon F. Majchrzak-Hong3 | Katherine Ness Shipley3 | Nicholas M. Salem3 | Ann I. Scher4 | Matthew R. Sapio5 | Michael J. Iadarola5 | Christopher E. Ramsden1,3  \n1Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, Maryland, USA | 2Department of Physical Medicine and Rehabilitation, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA | 3Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland, USA | 4Uniformed Services University of the Health Sciences, Bethesda, Maryland,  \nUSA | 5Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA Correspondence: Daisy Zamora ([zamora@unc.edu](zamora@unc.edu))  \nReceived: 16 June 2025 | Revised: 12 September 2025 | Accepted: 15 September 2025  \nFunding: This work was supported by by the following NIH intramural programs: National Institute on Aging (NIA), NIAAA, and National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided as a research gift from John M. Davis to the Laboratory of Clinical Investigation, NIA, and the University of North Carolina, Department of Physical Medicine and Rehabilitation. HBCC is supported by the Intramural Research Program at NIMH under project ZIC MH002903 .  \nKeywords: fatty acids | headache | meninges | migraine | oxylipins | trigeminal nerve  \nABSTRACT  \nOmega-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 (\u003C 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.  \n1 | Introduction  \nOmega-3 and omega-6 polyunsaturated fatty acids (PUFAs), which are major components of lipid membranes in human tissues, serve as precursors to oxylipins that modulate pain and inflammation and are implicated in headache pathogenesis (Ramsdenet al. 2021). In preclinical models, oxylipins derived from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)  \nexhibit anti-nociceptive and anti-inflammatory properties (Dyallet al. 2022). In contrast, oxylipins derived from omega-6 arachidonic acid (AA), such as prostaglandins and leukotrienes, have well-established pro-nociceptive, pro-inflammatory, and vasodilatory properties (Dyall et al. 2022). Emerging preclinical and clinical evidence also implicates oxylipin derivatives of omega-6 linoleic acid (LA) in pain signaling (Patwardhan et al. 2009; Boyd et al. 2021; Doolen et al. 2020; Domenichiello et al. ","cbCaijs2MfDYmTOF","https://ap.wps.com/l/cbCaijs2MfDYmTOF","pdf",1090092,"English","# Abstract\n## Introduction\n## Methods and Analysis (Regression Models)\n## Results (Blood–Tissue Associations)\n## Conclusion (Blood as a Tissue Proxy)","[{\"question\":\"What biological pathway links omega-3/omega-6 PUFAs to headache-related pain?\",\"answer\":\"Omega-3 and omega-6 PUFAs are precursors to oxylipins that modulate pain and inflammation. The paper also discusses potential mechanisms involving trigeminal ganglia receptors and TRP channel–related signaling that can influence headache processes.\"},{\"question\":\"How did the study compare PUFA precursor levels between blood and trigeminovascular tissues?\",\"answer\":\"The study quantified precursor PUFA compositions in post-mortem blood and trigeminovascular tissue specimens from 70 individuals. Regression models adjusted for confounders assessed relationships between blood and tissue PUFA levels.\"},{\"question\":\"Which blood fatty acid showed associations with trigeminovascular tissue levels?\",\"answer\":\"Eicosapentaenoic acid (EPA) in blood was associated with PUFA levels in cranial arteries, meninges, and trigeminal ganglia. Other listed PUFAs, including linoleic acid and arachidonic acid, also showed significant blood–tissue associations in meninges and/or trigeminal ganglia.\"}]","Associations Between Fatty Acid Levels in Human Blood and Trigeminovascular Tissues | PDF",1790752434,23]