Migraine headache model

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Headache disorders consistently rank as one of the most prevalent neurological conditions globally, with migraine being one of the most disabling disorders. 

Though the mechanism of migraine is complex and unresolved, one hypothesis states repeated activation of the trigeminal vascular system leads to long-term physiological changes.  Clinical symptoms include trigeminal allodynia and sensitivity to nitrates, both resulting in pain. A rat model of this pathology has been described by Oshinsky et al (2012). Melior has established and validated the Oshinsky model as a clinically translatable migraine animal model.

Proportional effects on periorbital von Frey thresholds relative to pretreatment baseline.

After four weeks of prostaglandin infusions directly onto the dura, rats exhibit chronic periorbital allodynia and nitrate sensitivity measured by mechanical von Frey fibers. Following prostaglandin sensitization, rats are challenged with vehicle-only, glycerol trinitrate (GTN) and vehicle, or GTN and sumatriptan (potent vasoconstrictor).

The figure shows the proportional effects on periorbital von Frey thresholds relative to an individual’s pretreatment baseline (proportional change in threshold; mean ± SEM).

The periorbital thresholds of rats dosed with GTN, Vehicle were significantly reduced compared to baseline thresholds at the 1.5 and 2.5 hour marks, confirming GTN sensitivity. Periorbital thresholds were significantly increased in animals dosed with GTN and sumatriptan, demonstrating that sensitivity to GTN was successfully blocked by administration of sumatriptan. No significant change was recorded in animals given vehicle.
Data are mean ± SEM; *p<0.05, ***p<0.001 compared to same group baseline. (N=9).

The prostaglandin-induced migraine animal model generally takes at least 6 weeks to complete when factoring in baseline measurements that are performed prior to surgery. Once migraine has been established animals can be used for an additional 4-5 weeks. Therefore, it is possible to test multiple compounds, with a “washout” between compounds, using a given cohort of animals.

Reference

Oshinsky ML, Sanghvi MM, Maxwell CR, Gonzalez D, Spangenberg RJ, Cooper M, Silberstein SD. (2012).  Spontaneous trigeminal allodynia in rats: a model of primary headache.  Headache.52(9):1336-49.