Current Pain and Headache Reports

, Volume 16, Issue 1, pp 110–115 | Cite as

Pathophysiology of Medication-overuse Headache: Implications from Animal Studies

  • Saknan Bongsebandhu-phubhakdi
  • Anan SrikiatkhachornEmail author
Chronic Daily Headache (SJ Wang, Section Editor)


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.


Analgesics Calcitonin gene–related peptide Cortical spreading depression Ergot Headache Medication overuse headache Migraine Nitric oxide Nociception Serotonin Substance P Tension-type headache Trigeminal system Triptans 



This study was supported by the Neuroscience of Headache Research Unit, the Thailand Research Fund (RTA5180004 and MRG5280061) and the Ratchadapiseksompotch Fund from the Faculty of Medicine, Chulalongkorn University.


No potential conflicts of interest relevant to this article were reported


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Saknan Bongsebandhu-phubhakdi
    • 1
  • Anan Srikiatkhachorn
    • 1
    Email author
  1. 1.Neuroscience Unit, Department of Physiology, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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