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.
Highlights
IntroductionThe mechanisms underlying the progression of migraine from an episodic to a chronic process are poorly understood, and the development of new therapies for chronic migraine has been slow, in part due to the lack of clinically relevant animal models
The mechanisms underlying the progression of migraine from an episodic to a chronic process are poorly understood, and the development of new therapies for chronic migraine has been slow, in part due to the lack of clinically relevant animal models.pronounced at 3 hours compared to baseline or immediately after rTMS
Pronounced at 3 hours compared to baseline or immediately after rTMS
Summary
The mechanisms underlying the progression of migraine from an episodic to a chronic process are poorly understood, and the development of new therapies for chronic migraine has been slow, in part due to the lack of clinically relevant animal models. Pronounced at 3 hours compared to baseline or immediately after rTMS. In the QPI group (n=11), we found a post-stimulation reduction of 1st block amplitude, which increased with time and was greater at 3 hours than immediately after the stimulation. No significant effect was found for the TBI and QPE protocols
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