title: The effects of acute and preventive migraine therapies in a mouse model of chronic migraine.
abstract: Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine-preventive treatments. Methods Migraine therapies were administered to male and female mice for 11 days. On day 3, mice were tested with nitroglycerin every second day for nine days. Basal and nitroglycerin-evoked mechanical hypersensitivity was evaluated using von Frey filaments. Results Chronic intermittent nitroglycerin produced acute hyperalgesia with each administration, and progressive and sustained basal hypersensitivity. The established preventive migraine therapy propranolol effectively blocked the development of acute and chronic nitroglycerin-induced hyperalgesia, while valproate had no effect. Potential migraine-preventive therapies were also tested: Amiloride inhibited nitroglycerin-induced acute and chronic hyperalgesia; while memantine was ineffective. We also tested the acute migraine therapy sumatriptan, which did not alter nitroglycerin-induced hyperalgesia, but instead resulted in acute and chronic hyperalgesia similar to that observed following nitroglycerin administration. Conclusions This study establishes the chronic nitroglycerin model as an additional screening tool to test novel migraine-preventive therapies.
authors.affiliation: 1 Department of Psychiatry, University of Illinois at Chicago, USA.
authors.forename: Alycia F
authors.initials: AF
authors.lastname: Tipton
authors.affiliation: 2 Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine, UCLA, USA.
authors.forename: Igal
authors.initials: I
authors.lastname: Tarash
authors.affiliation: 2 Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine, UCLA, USA.
authors.forename: Brenna
authors.initials: B
authors.lastname: McGuire
authors.affiliation: 2 Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine, UCLA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Charles
authors.affiliation: 1 Department of Psychiatry, University of Illinois at Chicago, USA.
authors.forename: Amynah A
authors.initials: AA
authors.lastname: Pradhan
mesh_terms: D000208:Acute Disease; D000584:Amiloride / Q000008:administration & dosage; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D005996:Nitroglycerin; D010147:Pain Measurement / Q000187:drug effects; D011433:Propranolol / Q000008:administration & dosage*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage; D013045:Species Specificity; D018170:Sumatriptan / Q000008:administration & dosage*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000927:Anticonvulsants; D058825:Serotonin 5-HT1 Receptor Agonists; D014665:Vasodilator Agents; D014635:Valproic Acid; D000584:Amiloride; D018170:Sumatriptan; D011433:Propranolol; D005996:Nitroglycerin
keywords: Allodynia; pain; prophylactic; triptan