title: Pathophysiology of medication-overuse headache: implications from animal studies.
abstract: Recent animal experiments have shown that chronic medication exposure profoundly affects the function of several areas in the nervous system related to headache pathogenesis. These changes include upregulation of calcitonin gene-related peptide, substance P, and nitric oxide synthase in trigeminal ganglia; expansion of receptive field and decreased nociceptive threshold of central trigeminal neurons; decrease in diffuse noxious inhibitory control; and increased susceptibility to develop cortical spreading depression (CSD). These changes indicate an increase in excitability of cortical and trigeminal neurons. The neuronal hyperexcitability may be the result of derangement of a central, possibly serotonin (5-HT)-dependent, modulating control system. Experiments with animals with low 5-HT showed that the processes of CSD and trigeminal nociception are enhanced in this condition. Derangement in the central 5-HT-dependent modulating system as a result of chronic medication use may underlie the chronification of headache as observed in patients with medication-overuse headache.
authors.affiliation: Neuroscience Unit, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Patumwan, Bangkok, Thailand.
authors.forename: Saknan
authors.initials: S
authors.lastname: Bongsebandhu-phubhakdi
authors.forename: Anan
authors.initials: A
authors.lastname: Srikiatkhachorn
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D051271:Headache Disorders, Secondary / Q000378:metabolism / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D014276:Trigeminal Nerve / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists
references.citation: Headache. 2010 Jun;50(6):998-1004
references.pmid: 20618816
references.citation: Cephalalgia. 2010 Mar;30(3):272-84
references.pmid: 19614707
references.citation: Headache. 2011 Jul-Aug;51(7):1152-60
references.pmid: 21649655
references.citation: Cephalalgia. 2004 May;24(5):398-407
references.pmid: 15096229
references.citation: Ann Neurol. 2007 Jun;61(6):603-6
references.pmid: 17474110
references.citation: Headache. 2006 Jan;46(1):34-9
references.pmid: 16412149
references.citation: Headache. 1997 Sep;37(8):486-91
references.pmid: 9329230
references.citation: Headache. 2010 Feb;50(2):185-97
references.pmid: 20039957
references.citation: Cephalalgia. 2006 Oct;26(10):1225-33
references.pmid: 16961791
references.citation: Ann Neurol. 2010 Mar;67(3):325-37
references.pmid: 20373344
references.citation: Neurology. 2004 Apr 27;62(8):1338-42
references.pmid: 15111671
references.citation: Cephalalgia. 2004;24 Suppl 1:9-160
references.pmid: 14979299
references.citation: Neurobiol Dis. 2011 Feb;41(2):430-5
references.pmid: 20977938
references.citation: J Neurosci. 2009 Dec 16;29(50):15828-35
references.pmid: 20016098
references.citation: Ann Neurol. 2006 Apr;59(4):652-61
references.pmid: 16450381
references.citation: Psychopharmacology (Berl). 1999 Feb;142(1):61-7
references.pmid: 10102783
references.citation: Headache. 2006 May;46(5):766-72
references.pmid: 16643579
references.citation: Headache. 2009 Mar;49(3):375-82
references.pmid: 19220502
references.citation: Neuroscience. 2000;99(3):529-39
references.pmid: 11029544
references.citation: J Neurosci. 2002 Aug 1;22(15):6747-55
references.pmid: 12151554
references.citation: Headache. 2000 May;40(5):343-50
references.pmid: 10849027
references.citation: Cephalalgia. 1996 Oct;16(6):423-6
references.pmid: 8902251
references.citation: Cephalalgia. 2004 Jan;24(1):2-11
references.pmid: 14687006
references.citation: Cephalalgia. 2010 Sep;30(9):1101-9
references.pmid: 20713560
references.citation: Headache. 2002 Jul-Aug;42(7):566-74
references.pmid: 12482207
references.citation: Brain. 2010 Aug;133(Pt 8):2475-88
references.pmid: 20627971
references.citation: Headache. 1995 May;35(5):269-72
references.pmid: 7775190
references.citation: Neuroscience. 2002;115(2):441-53
references.pmid: 12421610