title: Characterization of a novel model of chronic migraine.
abstract: Chronic migraine is a disabling condition that affects hundreds of millions of individuals worldwide. The development of novel migraine treatments has been slow, in part as a result of a lack of predicative animal models. We have developed a new model of chronic migraine involving the use of nitroglycerin (NTG), a known migraine trigger in humans. Chronic intermittent administration of NTG to mice resulted in acute mechanical hyperalgesia with each exposure as well as a progressive and sustained basal hyperalgesia. This chronic basal hyperalgesia occurred in a dose-dependent fashion and persisted for days after cessation of NTG administration. NTG-evoked hyperalgesia was exacerbated by the phosphodiesterase 5 inhibitor sildenafil, also a human migraine trigger, consistent with nitric oxide as a primary mediator of this hyperalgesia. The acute but not the chronic basal hyperalgesia was significantly reduced by the acute migraine therapy sumatriptan, whereas both the acute and chronic hyperalgesia was significantly attenuated by the migraine preventive therapy topiramate. Chronic NTG-induced hyperalgesia is a mouse model that may be useful for the study of mechanisms underlying progression of migraine from an episodic to a chronic disorder, and for the identification and characterization of novel acute and preventive migraine therapies.
authors.affiliation: Semel Institute for Neuropsychiatry and Human Behavior, University of California, Los Angeles, USA Shirley and Stefan Hatos Center for Neuropharmacology, University of California, Los Angeles, USA Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, USA Department of Psychiatry, University of Illinois at Chicago, USA.
authors.forename: Amynah A
authors.initials: AA
authors.lastname: Pradhan
authors.forename: Monique L
authors.initials: ML
authors.lastname: Smith
authors.forename: Brenna
authors.initials: B
authors.lastname: McGuire
authors.forename: Igal
authors.initials: I
authors.lastname: Tarash
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Evans
authors.forename: Andrew
authors.initials: A
authors.lastname: Charles
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008881:Migraine Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D005996:Nitroglycerin / Q000633:toxicity; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D018170:Sumatriptan / Q000494:pharmacology / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000633:toxicity
chemical_list: D014665:Vasodilator Agents; D018170:Sumatriptan; D005620:Freund's Adjuvant; D005996:Nitroglycerin
keywords: Central sensitization; Headache; Hyperalgesia