The process may result from platelet activation or an altered endothelial or coagulopathic state (Cavestro et al., 2011 and Pezzini et al., 2007). While thrombosis and migraine may be comorbid, the usually microthrombotic events contribute to microinfarcts in this population and also major strokes, usually occurring in the posterior circulation. Increased responses to sensory stimuli in migraineurs are observed interictally and include pain (allodynia), phonophobia, photophobia, and osmophobia. All of these changes are as a consequence of maladaptation with Selleck OSI 906 the disease. With repeated attacks there is evidence of central sensitization of sensory systems. Acute allodynia (pain to a normally

nonnoxious stimulus) is present in over 50% of patients; interictal allodynia is present in over a quarter of patients, greater still in patients who have aura (Lovati et al., 2008). The lowering of the pain threshold with repeated attacks may then allow for further attacks that contribute http://www.selleckchem.com/products/Fulvestrant.html to chronification that is mediated in part by medication overuse (Zappaterra et al., 2011). During the interictal period, episodic and chronic migraineurs are more sensitive to thermal stimulation than nonmigraine controls (Schwedt et al., 2011). In children with migraine, quantitative sensory testing to tonic heat applied to the trigeminal area shows increased sensitivity (Zohsel et al., 2006). Thus, alteration in sensory processing reflects changes

in brain systems that are a consequence of migraine load. Some have suggested that cutaneous allodynia is associated with migraine progression (Bonavita and De Simone, 2010). Other systems also show central sensitization even during the interictal period: phonophobia, osmophobia (Sjöstrand et al., 2010), and photophobia (Purdy, 2011). Abnormal brain activity is present

in studies of allodynia (Burstein to et al., 2010), olfactory hypersensitivity (Demarquay et al., 2008), and photophobia (Denuelle et al., 2011), all showing increased excitability. Such changes point to significant functional rewiring of the brain. Perhaps disease progression (increased frequency of attacks), transformation, or chronification (transformation from episodic to chronic migraine) of the brain state from low-frequency episodic migraine to high-frequency episodic migraine and then to chronic migraine (Bigal and Lipton, 2011) is the sine-qua-non of a measure of allostatic load in this clinical condition. About 6% of migraineurs progress to high-frequency episodic headaches, characterized by 105–179 headache days/year (Bigal and Lipton, 2008). Three percent of individuals in the general population with infrequent episodic headache progress to chronic daily headache (CDH) each year, and approximately 2.5% of patients with episodic migraine develop new-onset chronic migraine (Manack et al., 2011). Given the approximately 8 per 1000 of the population (Lyngberg et al., 2005), or a one-year prevalence of episodic migraine in the US of nearly 12% (Lipton et al.