Editing Migraine (section)

==Cause==
The underlying cause of migraine is unknown.<ref name=Rob10>{{cite journal | vauthors = Robbins MS, Lipton RB | title = The epidemiology of primary headache disorders | journal = Seminars in Neurology | volume = 30 | issue = 2 | pages = 107–19 | date = April 2010 | pmid = 20352581 | doi = 10.1055/s-0030-1249220 | s2cid = 260317083 }}</ref> However, it is believed to be related to a mix of environmental and genetic factors.<ref name=Lulli2007/> Migraine runs in families in about two-thirds of cases<ref name=Bart10/> and rarely occur due to a single gene defect.<ref name="Schurk2012"/> While migraine attacks were once believed to be more common in those of high intelligence, this does not appear to be true.<ref name = "Rasmussen_2006" /> A number of [[mental disorder|psychological conditions]] are associated, including [[major depressive disorder|depression]], [[anxiety disorder|anxiety]], and [[bipolar disorder]].<ref name=HA26>''The Headaches'', pp. 246–247</ref>
[[File:Gray786.png|thumb|Intracranial [https://www.ncbi.nlm.nih.gov/books/NBK459244/ cavernous sinus]: a potential site where dilation of cerebral vessels can compress multiple cranial nerves.]]
Success of the surgical migraine treatment by [[Nerve decompression|decompression]] of extracranial sensory nerves adjacent to vessels<ref>{{cite journal | vauthors = Bink T, Duraku LS, Ter Louw RP, Zuidam JM, Mathijssen IM, Driessen C | title = The Cutting Edge of Headache Surgery: A Systematic Review on the Value of Extracranial Surgery in the Treatment of Chronic Headache | journal = Plastic and Reconstructive Surgery | volume = 144 | issue = 6 | pages = 1431–1448 | date = December 2019 | pmid = 31764666 | doi = 10.1097/PRS.0000000000006270 | s2cid = 208273535 }}</ref> suggests that people with migraine may have anatomical predisposition for neurovascular compression<ref>{{cite journal | vauthors = Szmyd B, Sołek J, Błaszczyk M, Jankowski J, Liberski PP, Jaskólski DJ, Wysiadecki G, Karuga FF, Gabryelska A, Sochal M, Tubbs RS, Radek M | title = The Underlying Pathogenesis of Neurovascular Compression Syndromes: A Systematic Review | language = English | journal = Frontiers in Molecular Neuroscience | volume = 15 | pages = 923089 | date = 2022-07-04 | pmid = 35860499 | pmc = 9289473 | doi = 10.3389/fnmol.2022.923089 | doi-access = free }}</ref> that may be caused by both intracranial and extracranial vasodilation due to migraine triggers.<ref>{{cite journal | vauthors = Macionis V | title = Neurovascular Compression-Induced Intracranial Allodynia May Be the True Nature of Migraine Headache: an Interpretative Review | journal = Current Pain and Headache Reports | volume = 27 | issue = 11 | pages = 775–791 | date = November 2023 | pmid = 37837483 | doi = 10.1007/s11916-023-01174-7 }}</ref> This, along with the existence of numerous cranial neural interconnections,<ref>{{cite journal | vauthors = Adair D, Truong D, Esmaeilpour Z, Gebodh N, Borges H, Ho L, Bremner JD, Badran BW, Napadow V, Clark VP, Bikson M | title = Electrical stimulation of cranial nerves in cognition and disease | journal = Brain Stimulation | volume = 13 | issue = 3 | pages = 717–750 | date = May 2020 | pmid = 32289703 | pmc = 7196013 | doi = 10.1016/j.brs.2020.02.019 }}</ref> may explain the multiple cranial nerve involvement and consequent diversity of migraine symptoms.<ref>{{cite journal | vauthors = Villar-Martinez MD, Goadsby PJ | title = Pathophysiology and Therapy of Associated Features of Migraine | journal = Cells | volume = 11 | issue = 17 | pages = 2767 | date = September 2022 | pmid = 36078174 | pmc = 9455236 | doi = 10.3390/cells11172767 | doi-access = free }}</ref>

===Genetics===
{{Main|Genetics of migraine}}

[[Twin study|Studies of twins]] indicate a 34–51% genetic influence on the likelihood of developing migraine.<ref name="Lulli2007" /> This genetic relationship is stronger for migraine with aura than for migraine without aura.<ref name="Olesen_2006" /> It is clear from family and [[Population studies|populations studies]] that migraine is a [[disease|complex disorder]], where numerous [[single-nucleotide polymorphism|genetic risk variants]] exist, and where each variant increases the risk of migraine marginally.<ref>{{cite journal | vauthors = Gormley P, Kurki MI, Hiekkala ME, Veerapen K, Häppölä P, Mitchell AA, Lal D, Palta P, Surakka I, Kaunisto MA, Hämäläinen E, Vepsäläinen S, Havanka H, Harno H, Ilmavirta M, Nissilä M, Säkö E, Sumelahti ML, Liukkonen J, Sillanpää M, Metsähonkala L, Koskinen S, Lehtimäki T, Raitakari O, Männikkö M, Ran C, Belin AC, Jousilahti P, Anttila V, Salomaa V, Artto V, Färkkilä M, Runz H, Daly MJ, Neale BM, Ripatti S, Kallela M, Wessman M, Palotie A | title = Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families | journal = Neuron | volume = 98 | issue = 4 | pages = 743–753.e4 | date = May 2018 | pmid = 29731251 | pmc = 5967411 | doi = 10.1016/j.neuron.2018.04.014 }}</ref><ref>{{cite journal | vauthors = Harder AV, Terwindt GM, Nyholt DR, van den Maagdenberg AM | title = Migraine genetics: Status and road forward | journal = Cephalalgia | volume = 43 | issue = 2 | pages = 3331024221145962 | date = February 2023 | pmid = 36759319 | doi = 10.1177/03331024221145962 | doi-access = free }}</ref> It is also known that having several of these risk variants increases the risk by a small to moderate amount.<ref name="Schurk2012" />

[[Single gene disorder]]s that result in migraine are rare.<ref name=Schurk2012>{{cite journal | vauthors = Schürks M | title = Genetics of migraine in the age of genome-wide association studies | journal = The Journal of Headache and Pain | volume = 13 | issue = 1 | pages = 1–9 | date = January 2012 | pmid = 22072275 | pmc = 3253157 | doi = 10.1007/s10194-011-0399-0 }}</ref> One of these is known as [[familial hemiplegic migraine]], a type of migraine with aura, which is inherited in an [[autosomal dominant]] fashion.<ref>{{cite journal | vauthors = de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM | title = Molecular genetics of migraine | journal = Human Genetics | volume = 126 | issue = 1 | pages = 115–32 | date = July 2009 | pmid = 19455354 | doi = 10.1007/s00439-009-0684-z | s2cid = 20119237 }}</ref><ref>{{cite journal | vauthors = Montagna P | title = Migraine genetics | journal = Expert Review of Neurotherapeutics | volume = 8 | issue = 9 | pages = 1321–30 | date = September 2008 | pmid = 18759544 | doi = 10.1586/14737175.8.9.1321 | s2cid = 207195127 }}</ref> Four genes have been shown to be involved in familial hemiplegic migraine.<ref name=Ducros2013>{{cite journal | vauthors = Ducros A | title = [Genetics of migraine] | journal = Revue Neurologique | volume = 169 | issue = 5 | pages = 360–71 | date = May 2013 | pmid = 23618705 | doi = 10.1016/j.neurol.2012.11.010 }}</ref> Three of these genes are involved in [[ion transport]].<ref name=Ducros2013/> The fourth is the [[axon]]al protein [[PRRT2]], associated with the [[exocytosis]] complex.<ref name=Ducros2013/> Another genetic disorder associated with migraine is [[CADASIL syndrome]] or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.<ref name=Amin2009/> One meta-analysis found a protective effect from [[angiotensin converting enzyme]] polymorphisms on migraine.<ref>{{cite journal | vauthors = Wan D, Wang C, Zhang X, Tang W, Chen M, Dong Z, Yu S | title = Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis | journal = The International Journal of Neuroscience | volume = 126 | issue = 5 | pages = 393–9 | date = 1 January 2016 | pmid = 26000817 | doi = 10.3109/00207454.2015.1025395 | s2cid = 34902092 }}</ref> The ''[[TRPM8]]'' gene, which codes for a [[Ion channel|cation channel]], has been linked to migraine.<ref>{{cite journal | vauthors = Dussor G, Cao YQ | title = TRPM8 and Migraine | journal = Headache | volume = 56 | issue = 9 | pages = 1406–1417 | date = October 2016 | pmid = 27634619 | pmc = 5335856 | doi = 10.1111/head.12948 }}</ref>

The common forms migraine are [[Polygenic trait|polygenetic]], where common variants of numerous genes contributes to the predisposition for migraine.  These genes can be placed in three categories increasing the risk of migraine in general, specifically migraine with aura, or migraine without aura.<ref>{{cite journal | vauthors = Bjornsdottir G, Chalmer MA, Stefansdottir L, Skuladottir AT, Einarsson G, Andresdottir M, Beyter D, Ferkingstad E, Gretarsdottir S, Halldorsson BV, Halldorsson GH, Helgadottir A, Helgason H, Hjorleifsson Eldjarn G, Jonasdottir A, Jonasdottir A, Jonsdottir I, Knowlton KU, Nadauld LD, Lund SH, Magnusson OT, Melsted P, Moore KH, Oddsson A, Olason PI, Sigurdsson A, Stefansson OA, Saemundsdottir J, Sveinbjornsson G, Tragante V, Unnsteinsdottir U, Walters GB, Zink F, Rødevand L, Andreassen OA, Igland J, Lie RT, Haavik J, Banasik K, Brunak S, Didriksen M, T Bruun M, Erikstrup C, Kogelman LJ, Nielsen KR, Sørensen E, Pedersen OB, Ullum H, Masson G, Thorsteinsdottir U, Olesen J, Ludvigsson P, Thorarensen O, Bjornsdottir A, Sigurdardottir GR, Sveinsson OA, Ostrowski SR, Holm H, Gudbjartsson DF, Thorleifsson G, Sulem P, Stefansson H, Thorgeirsson TE, Hansen TF, Stefansson K | title = Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura | journal = Nature Genetics | volume = 55 | issue = 11 | pages = 1843–1853 | date = November 2023 | pmid = 37884687 | pmc = 10632135 | doi = 10.1038/s41588-023-01538-0 }}</ref><ref>{{cite journal | vauthors = Hautakangas H, Winsvold BS, Ruotsalainen SE, Bjornsdottir G, Harder AV, Kogelman LJ, Thomas LF, Noordam R, Benner C, Gormley P, Artto V, Banasik K, Bjornsdottir A, Boomsma DI, Brumpton BM, Burgdorf KS, Buring JE, Chalmer MA, de Boer I, Dichgans M, Erikstrup C, Färkkilä M, Garbrielsen ME, Ghanbari M, Hagen K, Häppölä P, Hottenga JJ, Hrafnsdottir MG, Hveem K, Johnsen MB, Kähönen M, Kristoffersen ES, Kurth T, Lehtimäki T, Lighart L, Magnusson SH, Malik R, Pedersen OB, Pelzer N, Penninx BW, Ran C, Ridker PM, Rosendaal FR, Sigurdardottir GR, Skogholt AH, Sveinsson OA, Thorgeirsson TE, Ullum H, Vijfhuizen LS, Widén E, van Dijk KW, Aromaa A, Belin AC, Freilinger T, Ikram MA, Järvelin MR, Raitakari OT, Terwindt GM, Kallela M, Wessman M, Olesen J, Chasman DI, Nyholt DR, Stefánsson H, Stefansson K, van den Maagdenberg AM, Hansen TF, Ripatti S, Zwart JA, Palotie A, Pirinen M | title = Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles | journal = Nature Genetics | volume = 54 | issue = 2 | pages = 152–160 | date = February 2022 | pmid = 35115687 | doi = 10.1038/s41588-021-00990-0 | pmc = 8837554 }}</ref> Three of these genes, ''[[CALCA]]'', ''[[CALCB]]'', and ''[[HTR1F]]'' are already target for migraine specific treatments. Five genes are specific risk to migraine with aura, ''[[PALM|PALMD]]'', ''[[ABO blood group system|ABO]]'', ''[[LRRK2]], [[CACNA1A]]'' and ''PRRT2'', and 13 genes are specific to migraine without aura. Using the accumulated genetic risk of the common variations, into a so-called [[Polygenic score|polygenetic risk]], it is possible to assess e.g. the treatment response to triptans.<ref>{{Cite journal | vauthors = Mikol DD, Picard H, Klatt J, Wang A, Peng C, Stefansson K |date=2020-04-14 |title=Migraine Polygenic Risk Score Is Associated with Severity of Migraine – Analysis of Genotypic Data from Four Placebo-controlled Trials of Erenumab (1214) |url=https://www.neurology.org/doi/10.1212/WNL.94.15_supplement.1214 |journal=Neurology |volume=94 |issue=15_supplement |doi=10.1212/WNL.94.15_supplement.1214 |issn=0028-3878}}</ref><ref>{{cite journal | vauthors = Kogelman LJ, Esserlind AL, Francke Christensen A, Awasthi S, Ripke S, Ingason A, Davidsson OB, Erikstrup C, Hjalgrim H, Ullum H, Olesen J, Folkmann Hansen T | title = Migraine polygenic risk score associates with efficacy of migraine-specific drugs | journal = Neurology. Genetics | volume = 5 | issue = 6 | pages = e364 | date = December 2019 | pmid = 31872049 | pmc = 6878840 | doi = 10.1212/NXG.0000000000000364 }}</ref>

===Triggers===
Migraine may be induced by triggers, with some reporting it as an influence in a minority of cases<ref name=Bart10/> and others the majority.<ref name=Trigger09/> Many things such as fatigue, certain foods, alcohol, and weather have been labeled as triggers; however, the strength and significance of these relationships are uncertain.<ref name=Trigger09>{{cite journal | vauthors = Levy D, Strassman AM, Burstein R | title = A critical view on the role of migraine triggers in the genesis of migraine pain | journal = Headache | volume = 49 | issue = 6 | pages = 953–7 | date = June 2009 | pmid = 19545256 | doi = 10.1111/j.1526-4610.2009.01444.x | s2cid = 31707887 }}</ref><ref>{{cite journal | vauthors = Martin PR | title = Behavioral management of migraine headache triggers: learning to cope with triggers | journal = Current Pain and Headache Reports | volume = 14 | issue = 3 | pages = 221–7 | date = June 2010 | pmid = 20425190 | doi = 10.1007/s11916-010-0112-z | s2cid = 5511782 }}</ref> Most people with migraine report experiencing triggers.<ref>{{cite journal | vauthors = Pavlovic JM, Buse DC, Sollars CM, Haut S, Lipton RB | title = Trigger factors and premonitory features of migraine attacks: summary of studies | journal = Headache | volume = 54 | issue = 10 | pages = 1670–9 |year = 2014 | pmid = 25399858 | doi = 10.1111/head.12468 | s2cid = 25016889 }}</ref> Symptoms may start up to 24 hours after a trigger.<ref name=Bart10/>

Also, evidence shows a strong association between migraine and the quality of sleep, particularly poor subjective quality of sleep. The relationship seems to be bidirectional, as migraine frequency increases with low quality of sleep yet the underlying mechanism of this correlation remains poorly understood.<ref>{{cite journal | vauthors = Stanyer EC, Creeney H, Nesbitt AD, Holland PR, Hoffmann J | title = Subjective Sleep Quality and Sleep Architecture in Patients With Migraine: A Meta-analysis | journal = Neurology | volume = 97 | issue = 16 | pages = e1620–e1631 | date = October 2021 | pmid = 34551985 | pmc = 8548957 | doi = 10.1212/WNL.0000000000012701 }}</ref>

====Physiological aspects====
Common triggers quoted are stress, hunger, and fatigue (these equally contribute to [[tension headaches]]).<ref name=Trigger09/> Psychological stress has been reported as a factor by 50–80% of people.<ref name=Rad2013>{{cite journal | vauthors = Radat F | title = [Stress and migraine] | journal = Revue Neurologique | volume = 169 | issue = 5 | pages = 406–12 | date = May 2013 | pmid = 23608071 | doi = 10.1016/j.neurol.2012.11.008 }}</ref> Migraine has also been associated with [[post-traumatic stress disorder]] and abuse.<ref>{{cite journal | vauthors = Peterlin BL, Katsnelson MJ, Calhoun AH | title = The associations between migraine, unipolar psychiatric comorbidities, and stress-related disorders and the role of estrogen | journal = Current Pain and Headache Reports | volume = 13 | issue = 5 | pages = 404–12 | date = October 2009 | pmid = 19728969 | pmc = 3972495 | doi = 10.1007/s11916-009-0066-1 }}</ref> Migraine episodes are more likely to occur around [[menstruation]].<ref name="Rad2013"/> Other hormonal influences, such as [[menarche]], [[oral contraceptive]] use, [[pregnancy]], perimenopause, and [[menopause]], also play a role.<ref name=Chai2014>{{cite journal | vauthors = Chai NC, Peterlin BL, Calhoun AH | title = Migraine and estrogen | journal = Current Opinion in Neurology | volume = 27 | issue = 3 | pages = 315–24 | date = June 2014 | pmid = 24792340 | pmc = 4102139 | doi = 10.1097/WCO.0000000000000091 }}</ref> These hormonal influences seem to play a greater role in migraine without aura.<ref name = "Rasmussen_2006" /> Migraine episodes typically do not occur during the [[second trimester|second]] and [[third trimester]]s of pregnancy, or following menopause.<ref name=Amin2009/>

====Dietary aspects====
Between 12% and 60% of people report foods as triggers.<ref name=Finocchi>{{cite journal | vauthors = Finocchi C, Sivori G | title = Food as trigger and aggravating factor of migraine | journal = Neurological Sciences | volume = 33 | issue = Suppl 1 | pages = S77-80 | date = May 2012 | pmid = 22644176 | doi = 10.1007/s10072-012-1046-5 | s2cid = 19582697 }}</ref><ref>{{cite journal | vauthors = Rockett FC, de Oliveira VR, Castro K, Chaves ML, Perla A, Perry ID | title = Dietary aspects of migraine trigger factors | journal = Nutrition Reviews | volume = 70 | issue = 6 | pages = 337–56 | date = June 2012 | pmid = 22646127 | doi = 10.1111/j.1753-4887.2012.00468.x | doi-access = free }}</ref>

There are many reports<ref>{{cite journal | vauthors = Ghose K, Carroll JD | title = Mechanism of tyramine-induced migraine: similarity with dopamine and interactions with disulfiram and propranolol in migraine patients | journal = Neuropsychobiology | volume = 12 | issue = 2–3 | pages = 122–126 |year = 1984 | pmid = 6527752 | doi = 10.1159/000118123 }}</ref><ref>{{cite journal | vauthors = Moffett A, Swash M, Scott DF | title = Effect of tyramine in migraine: a double-blind study | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 35 | issue = 4 | pages = 496–499 | date = August 1972 | pmid = 4559027 | pmc = 494110 | doi = 10.1136/jnnp.35.4.496 }}</ref><ref>{{cite web |title=Tyramine and Migraines: What You Need to Know |url=https://www.excedrin.com/migraines/causes/tyramine-and-migraines/ |access-date=4 March 2022 |website=excedrin.com }}</ref><ref>{{cite book |title=Encyclopedia of Food Sciences and Nutrition |publisher=Academic Press |year=2003 |isbn=978-0-12-227055-0|edition=Second }}</ref><ref>{{cite journal |vauthors=Özturan A, Şanlıer N, Coşkun Ö |title=The Relationship Between Migraine and Nutrition |url=https://jag.journalagent.com/tjn/pdfs/TJN_22_2_44_50&#91;A&#93;.pdf |journal=Turk J Neurol |year=2016 |volume=22 |issue=2 |pages=44–50 |doi=10.4274/tnd.37132 |access-date=4 March 2022 |archive-date=23 August 2023 |archive-url=https://web.archive.org/web/20230823051112/https://jag.journalagent.com/tjn/pdfs/TJN_22_2_44_50%5BA%5D.pdf |url-status=live }}</ref> that [[tyramine]]&nbsp;– which is naturally present in chocolate, alcoholic beverages, most cheeses, processed meats, and other foods&nbsp;– can trigger migraine symptoms in some individuals. [[Monosodium glutamate]] (MSG) has been reported as a trigger for migraine,<ref>{{cite journal | vauthors = Sun-Edelstein C, Mauskop A | title = Foods and supplements in the management of migraine headaches | journal = The Clinical Journal of Pain | volume = 25 | issue = 5 | pages = 446–452 | date = June 2009 | pmid = 19454881 | doi = 10.1097/AJP.0b013e31819a6f65 |url=http://www.trigemin.com/download/food-and-supplements-in-migraine-management.pdf | url-status = dead | s2cid = 3042635 | citeseerx = 10.1.1.530.1223 | archive-url=https://web.archive.org/web/20170813031041/http://www.trigemin.com/download/food-and-supplements-in-migraine-management.pdf<!--archive-url is useful as it provides access, while DOI is paywalled--> | archive-date = 13 August 2017 }}</ref> but a systematic review concluded that "a causal relationship between MSG and headache has not been proven... It would seem premature to conclude that the MSG present in food causes headache".<ref>{{cite journal | vauthors = Obayashi Y, Nagamura Y | title = Does monosodium glutamate really cause headache? : a systematic review of human studies | journal = The Journal of Headache and Pain | volume = 17 | issue = 1 | pages = 54 | date = 17 May 2016 | pmid = 27189588 | pmc = 4870486 | doi = 10.1186/s10194-016-0639-4 | doi-access = free | title-link = doi }}</ref>

====Environmental aspects====
Migraines may be triggered by weather changes, including changes in temperature and barometric pressure.<ref>{{cite web |title=Why Climate Change Might Be Affecting Your Headaches |url=https://www.pennmedicine.org/news/news-blog/2023/may/headache-and-climate-change |website=www.pennmedicine.org}}</ref><ref>{{cite web |last1=Cioffi |first1=I. |last2=Farella |first2=M. |last3=Chiodini |first3=P. |last4=Ammendola |first4=L. |last5=Capuozzo |first5=R. |last6=Klain |first6=C. |last7=Vollaro |first7=S. |last8=Michelotti |first8=A. |title=Effect of weather on temporal pain patterns in patients with temporomandibular disorders and migraine |url=https://pubmed.ncbi.nlm.nih.gov/28244179/ |website=Journal of Oral Rehabilitation |pages=333–339 |doi=10.1111/joor.12498 |date=May 2017}}</ref>

A 2009 review on potential triggers in the indoor and outdoor environment previously concluded that while there were insufficient studies to confirm environmental factors as causing migraine, "migraineurs worldwide consistently report similar environmental triggers ... such as barometric pressure change, bright sunlight, flickering lights, air quality and odors".<ref name="Fri2009">{{cite journal |vauthors=Friedman DI, De ver Dye T |date=June 2009 |title=Migraine and the environment |journal=Headache |volume=49 |issue=6 |pages=941–52 |doi=10.1111/j.1526-4610.2009.01443.x |pmid=19545255 |doi-access=free |s2cid=29764274}}</ref>