Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats

Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats | 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 Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats Ming R. Wang, Ching J. Tseng, Jon S. Kuo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1776188/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Trigeminal autonomic cephalalgias (TACs) comprise cluster headaches and are characterized 19 by unilateral neuralgiform headache attacks associated with autonomic responses and somatic 2 20 responses. An animal model for evaluating the anatomical basis of the TAC-like response is 21 not currently available. Twenty-five rats weighing 550-650 g were anaesthetized with 22 urethane. The TAC-like response was produced either by subcutaneous injection of formalin 23 into the unilateral facial cheek or by electrical stimulation of the unilateral intact trigeminal 24 nerve. The induced TAC-like response, which included ipsilateral common carotid arterial 25 flow (iCCAF) and other autonomic responses, was studied in intact nerves or after cutting 26 either the ipsilateral trigeminal nerve or the ipsilateral facial nerve. The formalin injections 27 produced concentration-dependent iCCAF increases accompanied by ipsilateral autonomic 28 responses of rhinitis-like nasal congestion, nasal mucus, meiosis, lacrimation, red eye, and 29 eyelid oedema. The formalin (5% or 10%, 0.5 cc)-induced responses were nearly abolished 30 by sectioning of either the facial or trigeminal nerve. The electrical stimulation (15 V, 60 Hz, 31 and 0.4 ms) of the intact trigeminal nerve or its ophthalmo-maxillary branch also produced 32 stimulation strength-dependent iCCAF increases as well as autonomic responses; however, 33 the electrical stimulation-induced iCCAF increases and other autonomic responses could still 34 be induced by electrical stimulation of the central but not the peripheral end of the 35 ophthalmo-maxillary branch (n = 8) or the trigeminal nerve (n = 2). Thus, an animal model 36 for inducing the TAC-like response by subcutaneous formalin injection into the rat facial 37 cheek was established. The TAC-like response could be sequentially mediated via the 38 afferent trigeminal nerve, trigeminal nucleus, dorsal facial nucleus, and efferent facial nerve. Systems Biology Neurobiology of Disease Physiology Trigeminal autonomic cephalalgia-like responses Formalin pain test Ophthalmo-maxillary branch of the trigeminal nerve Facial nerve Common carotid arterial flow Autonomic responses Full Text Supplementary Files Additionalfile1autonomicresponses.pdf Fig.S4 Increases in iCCAF and autonomic responses (nasal mucus, eyelid oedema, red eye, meiosis, lacrimation) induced by injections 5%, 0.5 cc formalin into the facial cheek of anesthetized rats. Addditionalfile2COX2stained.pdf Fig. S4 COX-2 dense staining (brown colour) in outer membrane of CCA which is a section the same CCA at approximately 180 min after marked increase (vasodilatation) in the CCAF was induced by formalin 10%, 0.5 cc into the facial-cheek in SD rat (n=6). Additionalfile3increaseiCCAFinDFAinrat.pdf Fig. S4 Microinjection of sodium glutamate (Glu, 0.1M, 400 nl) into the dorsal facial area (DFA) in SD rats cause the left common carotid blood flow (LCCAF) increases (3.3 to 6.5 cc), and it returns to normal in about 5 minutes. After 30 minutes, the same dose of stimulation will cause the same increase in LCCAF. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-1776188","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":115915130,"identity":"89747088-a03d-4cce-8413-e00c1345a3a9","order_by":0,"name":"Ming R. 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An animal model for evaluating the anatomical basis of the TAC-like response is 21 not currently available. Twenty-five rats weighing 550-650 g were anaesthetized with 22 urethane. The TAC-like response was produced either by subcutaneous injection of formalin 23 into the unilateral facial cheek or by electrical stimulation of the unilateral intact trigeminal 24 nerve. The induced TAC-like response, which included ipsilateral common carotid arterial 25 flow (iCCAF) and other autonomic responses, was studied in intact nerves or after cutting 26 either the ipsilateral trigeminal nerve or the ipsilateral facial nerve. The formalin injections 27 produced concentration-dependent iCCAF increases accompanied by ipsilateral autonomic 28 responses of rhinitis-like nasal congestion, nasal mucus, meiosis, lacrimation, red eye, and 29 eyelid oedema. The formalin (5% or 10%, 0.5 cc)-induced responses were nearly abolished 30 by sectioning of either the facial or trigeminal nerve. The electrical stimulation (15 V, 60 Hz, 31 and 0.4 ms) of the intact trigeminal nerve or its ophthalmo-maxillary branch also produced 32 stimulation strength-dependent iCCAF increases as well as autonomic responses; however, 33 the electrical stimulation-induced iCCAF increases and other autonomic responses could still 34 be induced by electrical stimulation of the central but not the peripheral end of the 35 ophthalmo-maxillary branch (n = 8) or the trigeminal nerve (n = 2). Thus, an animal model 36 for inducing the TAC-like response by subcutaneous formalin injection into the rat facial 37 cheek was established. The TAC-like response could be sequentially mediated via the 38 afferent trigeminal nerve, trigeminal nucleus, dorsal facial nucleus, and efferent facial nerve.\u003c/p\u003e","manuscriptTitle":"Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-07-15 19:50:24","doi":"10.21203/rs.3.rs-1776188/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2022-06-23 17:00:10","doi":"10.21203/rs.3.rs-1776188/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4f900e5f-da3d-4f33-afda-bfec8abd9bea","owner":[],"postedDate":"July 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":14043787,"name":"Systems Biology"},{"id":14043788,"name":"Neurobiology of Disease"},{"id":14043789,"name":"Physiology"}],"tags":[],"updatedAt":"2022-06-23T17:00:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-15 19:50:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-1776188","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1776188","identity":"rs-1776188","version":["v2"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}