Editing Headache (section)

== Pathophysiology ==
The [[Human brain|brain]] itself is not sensitive to [[pain]], because it lacks [[nociceptor|pain receptor]]s. However, several areas of the [[head]] and [[neck]] do have pain receptors and can thus sense pain. These include the extracranial arteries, [[middle meningeal artery]], large veins, [[venous sinuses]], cranial and spinal nerves, head and neck muscles, the [[meninges]], [[falx cerebri]], parts of the brainstem, eyes, ears, teeth, and lining of the mouth.<ref name=ACEP2008>{{cite journal | vauthors = Edlow JA, Panagos PD, Godwin SA, Thomas TL, Decker WW | title = Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute headache | journal = Annals of Emergency Medicine | volume = 52 | issue = 4 | pages = 407–436 | date = October 2008 | pmid = 18809105 | doi = 10.1016/j.annemergmed.2008.07.001 | s2cid = 507361 }}</ref><ref name="Clinical Neurology">{{cite book|vauthors = Greenberg D, Aminoff M, Simon R|title=Clinical Neurology 8/E:Chapter 6. Headache & Facial Pain|date=6 May 2012|publisher=McGraw Hill Professional|isbn=978-0-07-175905-2}}</ref> Pial arteries, rather than pial veins are responsible for pain production.<ref name="Goadsby" />

Headaches often result from traction or irritation of the meninges and blood vessels.<ref>{{Cite web |title=headache {{!}} Britannica |url=https://www.britannica.com/science/headache |access-date=2022-04-29 |website=www.britannica.com |language=en}}</ref> The pain receptors may be stimulated by head trauma or tumours and cause headaches. Blood vessel spasms, dilated [[blood vessels]], inflammation or infection of meninges and muscular tension can also stimulate pain receptors.<ref name="Clinical Neurology" /> Once stimulated, a [[nociceptor]] sends a message up the length of the nerve fibre to the nerve cells in the brain, signalling that a part of the body hurts.<ref>{{cite journal | vauthors = Dubin AE, Patapoutian A | title = Nociceptors: the sensors of the pain pathway | journal = The Journal of Clinical Investigation | volume = 120 | issue = 11 | pages = 3760–3772 | date = November 2010 | pmid = 21041958 | pmc = 2964977 | doi = 10.1172/JCI42843 }}</ref>

Primary headaches are more difficult to understand than secondary headaches. The exact mechanisms which cause migraines, tension headaches and cluster headaches are not known.<ref name="Leroux"/> There have been [[Migraine#Cause|different hypotheses]] over time that attempt to explain what happens in the brain to cause these headaches.<ref>{{Cite web|title=How a Migraine Happens|url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/headache/how-a-migraine-happens|access-date=2021-12-18|website=www.hopkinsmedicine.org|date=26 November 2019 |language=en}}</ref>

Migraines are currently thought to be caused by dysfunction of the nerves in the brain.<ref name="uptodate">{{cite web | vauthors = Cutrer FM, Bajwa A, Sabhat M | title = Pathophysiology, clinical manifestations and diagnosis of migraine in adults. | work = UpToDate | veditors = Post TW | location = San Francisco, CA | publisher = Wolters Kluwer | access-date = 23 April 2014 | url = https://www.uptodate.com/contents/pathophysiology-clinical-manifestations-and-diagnosis-of-migraine-in-adults }}</ref> Previously, migraines were thought to be caused by a primary problem with the blood vessels in the brain.<ref>{{cite journal | vauthors = Goadsby PJ | title = The vascular theory of migraine--a great story wrecked by the facts | journal = Brain | volume = 132 | issue = Pt 1 | pages = 6–7 | date = January 2009 | pmid = 19098031 | doi = 10.1093/brain/awn321 | doi-access = free }}</ref> This vascular theory, which was developed in the 20th century by Wolff, suggested that the aura in [[migraines]] is caused by constriction of intracranial vessels (vessels inside the brain), and the headache itself is caused by rebound dilation of extracranial vessels (vessels just outside the brain). Dilation of these extracranial blood vessels activates the pain receptors in the surrounding nerves, causing a headache. The vascular theory is no longer accepted.<ref name="uptodate" /><ref name="Charles">{{cite journal | vauthors = Charles A | title = Vasodilation out of the picture as a cause of migraine headache | journal = The Lancet. Neurology | volume = 12 | issue = 5 | pages = 419–420 | date = May 2013 | pmid = 23578774 | doi = 10.1016/s1474-4422(13)70051-6 | s2cid = 42240966 }}</ref>  Studies have shown migraine head pain is not accompanied by extracranial vasodilation, but rather only has some mild intracranial vasodilation.<ref name="Amin">{{cite journal | vauthors = Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, de Koning PJ, Larsson HB, Olesen J, Ashina M | title = Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study | journal = The Lancet. Neurology | volume = 12 | issue = 5 | pages = 454–461 | date = May 2013 | pmid = 23578775 | doi = 10.1016/S1474-4422(13)70067-X | s2cid = 25553357 }}</ref>

Currently, most specialists think migraines are due to a primary problem with the nerves in the brain.<ref name="uptodate" /> Auras are thought to be caused by a wave of increased activity of neurons in the [[cerebral cortex]] (a part of the brain) known as cortical spreading depression<ref name="pmid11287655">{{cite journal | vauthors = Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RB, Sorensen AG, Moskowitz MA | title = Mechanisms of migraine aura revealed by functional MRI in human visual cortex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 8 | pages = 4687–4692 | date = April 2001 | pmid = 11287655 | pmc = 31895 | doi = 10.1073/pnas.071582498 | doi-access = free | bibcode = 2001PNAS...98.4687H }}</ref> followed by a period of depressed activity.<ref>{{cite journal | vauthors = Buzzi MG, Moskowitz MA | title = The pathophysiology of migraine: year 2005 | journal = The Journal of Headache and Pain | volume = 6 | issue = 3 | pages = 105–111 | date = June 2005 | pmid = 16355290 | pmc = 3451639 | doi = 10.1007/s10194-005-0165-2 }}</ref> Some people think headaches are caused by the activation of [[sensory nerves]] which release peptides or [[serotonin]], causing inflammation in arteries, dura and  meninges and also cause some vasodilation. [[Triptan]]s, medications that treat migraines, block serotonin receptors and constrict blood vessels.<ref>{{cite book|chapter-url=http://accessmedicine.mhmedical.com/content.aspx?bookid=348&sectionid=40381638| vauthors = Denny CJ, Schull MJ | chapter = Chapter 159. Headache and Facial Pain. | veditors = Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD | title = Tintinalli's Emergency Medicine: A Comprehensive Study Guide | edition = 7th | location = New York, NY | publisher = The McGraw-Hill Companies | date = 2011 |url-status=dead |archive-url= https://web.archive.org/web/20150531030337/http://accessmedicine.mhmedical.com/content.aspx?bookid=348&sectionid=40381638 |archive-date=31 May 2015 |access-date=30 May 2015}}</ref>

People who are more susceptible to experiencing migraines without headaches are those who have a family history of migraines, women, and women who are experiencing hormonal changes or are taking [[birth control pills]] or are prescribed [[Hormone replacement therapy (menopause)|hormone replacement therapy]].<ref>{{cite web|title=Migraine Without Headache|url=http://www.neurobalancechiropractic.com.au/migraine-without-headache/|publisher=Neurobalance|access-date=16 July 2014|url-status=live|archive-url= https://web.archive.org/web/20150108113836/http://www.neurobalancechiropractic.com.au/migraine-without-headache/ |archive-date=8 January 2015}}</ref>

[[Tension headaches]] are thought to be caused by the activation of peripheral nerves in the head and neck muscles.<ref name="Loder">{{cite journal | vauthors = Loder E, Rizzoli P | title = Tension-type headache | journal = BMJ | volume = 336 | issue = 7635 | pages = 88–92 | date = January 2008 | pmid = 18187725 | pmc = 2190284 | doi = 10.1136/bmj.39412.705868.ad }}</ref>

[[Cluster headaches]] involve overactivation of the [[trigeminal nerve]] and [[hypothalamus]] in the brain, but the exact cause is unknown.<ref name="Leroux">{{cite journal | vauthors = Leroux E, Ducros A | title = Cluster headache | journal = Orphanet Journal of Rare Diseases | volume = 3 | issue = 1 | pages = 20 | date = July 2008 | pmid = 18651939 | pmc = 2517059 | doi = 10.1186/1750-1172-3-20 | doi-access = free }}</ref><ref>{{Cite book |last=Levin |first=Emily Lehmann |title=Pain Neurosurgery |chapter-url=https://oxfordmedicine.com/view/10.1093/med/9780190887674.001.0001/med-9780190887674-chapter-16 |chapter=Cluster Headache |year=2019 |pages=125–130 |publisher=Oxford University Press |isbn=978-0-19-088770-4 |language=en-US |doi=10.1093/med/9780190887674.003.0016}}</ref>