197 In one animal study

it was shown that triptans disrupted communication between peripheral and central trigeminovascular neurons.198 In a group of 28 migraine patients with allodynia treated 4 hours after onset, subcutaneous sumatriptan was ineffective in 14 patients. These patients were subsequently treated i.v. with the COX1/COX2 inhibitor ketorolac as were 14 other allodynic patients.199 A PF state was observed in 71% and 64%, respectively.199 In animal studies COX1/COX2 inhibitors, ketorolac, indomethacin, and naproxen, can exert inhibition of the central trigeminovascular small molecule library screening neurons and can suppress central sensitization in rats.200 In contrast, subcutaneous sumatriptan was equally effective when given early (62% PF after 2 hours) or late (55% PF after 2 hours) during migraine attacks in one open study (n = 20).201 In an unpublished RCT (n = 90) both early and late (4 hours) treatment of migraine attacks HM781-36B price with subcutaneous sumatriptan 6 mg resulted in headache relief in about 80% in both groups.201 In addition, subcutaneous naratriptan 10 mg in an RCT

resulted in 88% of patients (n = 34) being PF after 2 hours even if more that 50% were treated after 4 hours.202,203 These 2 studies indicate that parenteral triptans are equally effective when used early or late in the treatment of migraine attacks. Another way to circumvent the problem of allodynia is to treat early which makes common sense. In one prospective, placebo-controlled RCT with almotriptan 12.5 mg it was demonstrated that early (<1 hour) and mild headache treatment (53% PF) was superior

to treatment of moderate or severe headache (38% PF).204 Citations of Highlighted Papers.— There was comparable, and reasonable, agreement between ISI Web of Knowledge and Google Scholar (see Table 2). The 2 papers with most citations, are Leão’s paper (1129) on CSD10 and the Leiden Group’s paper (1215) on the gene for FHM1.19 In this review we tried to highlight the major clinical and scientific observations of migraine from 1910 to 2010. This was undertaken from the present perspective check details and therefore observations that may have seemed important in the past may have been omitted, although we believe we have touched upon the main areas that have occupied migraine investigators. After the discovery of ergotamine in the late 19th century, its isolation in the early 20th century led to rather primitive trials (from today’s perspective) as well as research on the pathogenesis of migraine. American research of therapeutics in the 1930s seemed more thorough than the early European endeavors.