MERTK in the trigeminal system: a novel target for cluster headache and other headache disorders?

MERTK in the trigeminal system: a novel target for cluster headache and other headache disorders? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article MERTK in the trigeminal system: a novel target for cluster headache and other headache disorders? Jacob Carl Alexander Edvinsson, Lars Edvinsson, Caroline Ran, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4281019/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 May, 2024 Read the published version in The Journal of Headache and Pain → Version 1 posted 11 You are reading this latest preprint version Abstract The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand Galectin-3 has been found to be elevated in serum in migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and Galectin-3 expression in rodent trigeminal ganglia (TG). RT-qPCR was used to assess MERTK gene expression in blood and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache patients as compared to controls. In addition, MERTK ligand Galectin-3 was found at increased concentration in the serum of study participants with cluster headache, while the ligands Growth Arrest Specific 6 and protein S levels were unaffected. MERTK and Galectin-3 were both expressed in rat TG. Galectin-3 was primarily located to smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells (SGC) and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and Galectin-3 in study participants with cluster headache, as well as the presence of MERTK in peripheral SGC and Schwann cells in the TG, further highlights MERTK signalling as an interesting therapeutic target in primary headache. Trigeminal system MER proto-oncogene tyrosine kinase migraine GWAS Galectin-3 Full Text Additional Declarations No competing interests reported. Supplementary Files Suppli.Table1AntibodiesMERTK.docx GraphicalAbstract.tif Cite Share Download PDF Status: Published Journal Publication published 22 May, 2024 Read the published version in The Journal of Headache and Pain → Version 1 posted Editorial decision: Revision requested 02 May, 2024 Reviews received at journal 01 May, 2024 Reviews received at journal 23 Apr, 2024 Reviewers agreed at journal 22 Apr, 2024 Reviews received at journal 21 Apr, 2024 Reviewers agreed at journal 20 Apr, 2024 Reviewers agreed at journal 18 Apr, 2024 Reviewers invited by journal 17 Apr, 2024 Editor assigned by journal 17 Apr, 2024 Submission checks completed at journal 17 Apr, 2024 First submitted to journal 17 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4281019","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":293587545,"identity":"49effbd4-5623-4f4a-abbf-33130225ab50","order_by":0,"name":"Jacob Carl Alexander 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