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No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild\u2010type Sprague\u2010Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.<\/jats:p>","DOI":"10.1111\/j.1526-4610.2012.02247.x","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T13:44:24Z","timestamp":1344001464000},"page":"1336-1349","source":"Crossref","is-referenced-by-count":62,"title":["Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache"],"prefix":"10.1111","volume":"52","author":[{"given":"Michael L.","family":"Oshinsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menka M.","family":"Sanghvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina R.","family":"Maxwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Spangenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marnie","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Silberstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,10]]},"reference":[{"issue":"2","key":"e_1_2_9_2_2","first-page":"S2","article-title":"Epidemiology, impact, and comorbidities of migraine headaches in the United States","volume":"60","author":"Lipton RB","year":"2003","journal-title":"Neurology"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05036.x"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.1995.1504277.x"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2004.06.008"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2009.01924.x"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0901s06"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01139.x"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2009.04.003"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282fc25de"},{"issue":"3","key":"e_1_2_9_11_2","first-page":"28","article-title":"Peripheral and central sensitization during migraine","volume":"15","author":"Malick A","year":"2000","journal-title":"Funct Neurol"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2006.00489.x"},{"key":"e_1_2_9_13_2","first-page":"9","article-title":"Experimental models of migraine","volume":"15","author":"Reuter U","year":"2000","journal-title":"Funct Neurol"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.10.006"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1586\/ern.10.16"},{"key":"e_1_2_9_16_2","first-page":"169","article-title":"Ictal and interictal hypoactivation of the occipital cortex in migraine with aura. 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