Editing Cluster headache (section)

==Causes==
{| class="wikitable floatright"
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| [[Image:PET1.jpg|center|150x150px]] || [[Image:PET2.jpg|center|150x150px]] || [[Image:PET3.jpg|center|150x150px]]
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| colspan="3" style="text-align:center;"| [[Positron emission tomography]] (PET) shows brain areas being activated during pain.
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| [[Image:VBM1.jpg|center|150x150px]] || [[Image:VBM2.jpg|center|150x150px]] || [[Image:VBM3.jpg|center|150x150px]]
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| colspan="3" style="text-align:center;"| [[Voxel-based morphometry]] shows brain area structural differences.
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The specific causes and pathogenesis of cluster headaches are not fully understood.<ref name=":2" /> The Third Edition of the International Classification of Headache disorders classifies cluster headaches as belonging to the [[Trigeminal autonomic cephalgia|trigeminal autonomic cephalalgias]].<ref>{{cite journal |author=Headache Classification Committee of the International Headache Society (IHS) |s2cid=78846027 |date=2013 |title=The International Classification of Headache Disorders, 3rd edition (beta version) |journal=Cephalalgia |volume=33 |issue=9 |pages=629–808 |doi=10.1177/0333102413485658 |pmid=23771276 |url=https://www.zora.uzh.ch/id/eprint/89115/1/89115.pdf |access-date=16 August 2019 |archive-date=9 February 2020 |archive-url=https://web.archive.org/web/20200209062132/https://www.zora.uzh.ch/id/eprint/89115/1/89115.pdf |url-status=live }}</ref>

Some experts consider the posterior [[hypothalamus]] to be important in the pathogenesis of cluster headaches. This is supported by a relatively high success ratio of [[Deep brain stimulation|deep-brain stimulation therapy]] on the posterior hypothalamic [[grey matter]].<ref name=":2" />

===Nerves===
Therapies acting on the [[vagus nerve]] ([[cranial nerve]] X) and the [[greater occipital nerve]] have both shown efficacy in managing cluster headache, but the specific roles of these nerves are not well-understood.<ref name=":2" /> Two nerves thought to play an important role in cluster headaches include the trigeminal nerve and the [[facial nerve]].<ref name="image">{{cite journal |vauthors =Ferraro S, Nigri A, Bruzzone MG, Demichelis G, Pinardi C, Brivio L, Giani L, Proietti A, Leone M, Chiapparini L| s2cid =91190597 | title =Cluster headache: insights from resting-state functional magnetic resonance imaging | journal = Neurological Sciences| date = 2019 | volume =40| issue =Suppl 1| pages =45–47| doi =10.1007/s10072-019-03874-8| pmid = 30941629}}</ref>

===Genetics===
Cluster headache may run in some families in an [[autosomal dominant]] inheritance pattern.<ref name="updateongenetics">{{cite journal |vauthors=Waung MW, Taylor A, Qualmann KJ, Burish MJ| title = Family History of Cluster HeadacheA Systematic Review | journal = JAMA Neurology| date = 2020 | volume = 77 | issue = 7 | pages = 887–896 | doi = 10.1001/jamaneurol.2020.0682 | pmid = 32310255 | pmc = 7644512 }}</ref><ref name="Pinessi2005">{{cite journal |last1=Pinessi |first1=L. |last2=Rainero |first2=I. |last3=Rivoiro |first3=C. |last4=Rubino |first4=E. |last5=Gallone |first5=S. |year=2005 |title=Genetics of cluster headache: An update |journal=[[The Journal of Headache and Pain]] |volume=6 |issue=4 |pages=234–6 |doi=10.1007/s10194-005-0194-x |pmc=3452030 |pmid=16362673}}</ref> People with a [[Consanguinity|first degree relative]] with the condition are about 14–48 times more likely to develop it themselves,<ref name=Nesbitt2012 /> and around 8 to 10% of persons with cluster headaches have a family history.<ref name="updateongenetics" /><ref name=":0">{{Cite journal|last1=O'Connor|first1=Emer|last2=Simpson|first2=Benjamin S.|last3=Houlden|first3=Henry|last4=Vandrovcova|first4=Jana|last5=Matharu|first5=Manjit|date=2020-04-25|title=Prevalence of familial cluster headache: a systematic review and meta-analysis|journal=[[The Journal of Headache and Pain]]|volume=21|issue=1|pages=37|doi=10.1186/s10194-020-01101-w|issn=1129-2377|pmc=7183702|pmid=32334514 |doi-access=free }}</ref> Several studies have found a higher number of relatives affected among females.<ref name=":0" /> Others have suggested these observations may be due to lower numbers of females in these studies.<ref name=":0" /> Possible genetic factors warrant further research, current evidence for genetic inheritance is limited.<ref name=Pinessi2005 />

Genes that are thought to play a role in the disease are the hypocretin/orexin receptor type 2 (HCRTR2), alcohol dehydrogenase 4(ADH4), G protein beta 3 (GNB3), pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1), and membrane metalloendopeptidase (MME) genes.<ref name="updateongenetics" />

===Tobacco smoking===
About 65% of persons with cluster headache are, or have been, tobacco smokers.<ref name=Nesbitt2012 /> Stopping smoking does not lead to improvement of the condition, and cluster headaches also occur in those who have never smoked (e.g., children);<ref name=Nesbitt2012 /> it is thought unlikely that smoking is a cause.<ref name=Nesbitt2012 /> People with cluster headaches may be predisposed to certain traits, including smoking or other lifestyle habits.<ref name="pmid18474191">{{cite journal |doi=10.1007/s11916-008-0022-5 |pmid=18474191 |title=Cluster headache and lifestyle habits |journal=Current Pain and Headache Reports |volume=12 |issue=2 |pages=115–21 |year=2008 |last1=Schürks |first1=Markus |last2=Diener |first2=Hans-Christoph |s2cid=29434840 }}</ref>

===Hypothalamus===
A review suggests that the [[suprachiasmatic nucleus]] of the [[hypothalamus]], which is the major biological clock in the human body, may be involved in cluster headaches, because cluster headaches occur with diurnal and seasonal rhythmicity.<ref>{{cite journal |last=Pringsheim |first=Tamara |title=Cluster headache: evidence for a disorder of circadian rhythm and hypothalamic function |journal=Canadian Journal of Neurological Sciences |date=February 2002 |volume=29 |issue=1 |pages=33–40 |doi=10.1017/S0317167100001694 |pmid=11858532|doi-access=free }}</ref>

[[Positron emission tomography]] (PET) scans indicate the brain areas which are activated during attack only, compared to pain free periods. These pictures show brain areas that are active during pain in yellow/orange color (called "pain matrix"). The area in the center (in all three views) is activated only during cluster headaches. The bottom row [[voxel-based morphometry]] shows structural brain differences between individuals with and without CH; only a portion of the [[hypothalamus]] is different.<ref>{{cite journal |doi=10.1007/s11916-007-0010-1 |pmid=17367592 |title=Cluster headache: A review of neuroimaging findings |journal=Current Pain and Headache Reports |volume=11 |issue=2 |pages=131–6 |year=2007 |last1=Dasilva |first1=Alexandre F. M. |last2=Goadsby |first2=Peter J. |last3=Borsook |first3=David |s2cid=35178080 }}</ref>