Characterization of a novel model of chronic migraine.

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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.

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Author and article information

Journal

Journal ID (iso-abbrev): Pain

Title: Pain

ISSN (Electronic): 1872-6623

ISSN (Print): 0304-3959

Publication date (Electronic): Feb 2014

Volume: 155

Issue: 2

Affiliations

[1 ] 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. Electronic address: apradhan@psych.uic.edu.

[2 ] 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.

[3 ] 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.

[4 ] 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.

Article

Publisher Item ID: S0304-3959(13)00543-5 Mid ID: NIHMS541987

DOI: 10.1016/j.pain.2013.10.004

PubMed ID: 24121068

SO-VID: 0ea2c85f-b1f3-4fa6-9941-95191927102e

History

Keywords: Central sensitization,Headache,Hyperalgesia

Data availability:

Keywords: Central sensitization, Headache, Hyperalgesia

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