Models & Assays
Migraine
We have validated that the pituitary adenylate-cyclase-activating polypeptide-38 (PACAP-38) can induce both periorbital and plantar mechanical allodynia in our rat model and this can successfully be reversed using PA-8 (a PAC1 receptor antagonist).
We have validated that the calcitonin gene-related peptide (CGRP) can induce acute migraine including both plantar and periorbital mechanical allodynia in our rat model and this can successfully be reversed using Sumatriptan.
Glyceryl trinitrate (GTN) infusion triggers episodes in about 80% of migraineurs and this can be replicated in rodents; a single GTN administration in rats triggers transient mechanical hypersensitivity at both the periorbital (around the eye socket) and plantar areas, which can be reversed by sumatriptan. Repeated GTN administration triggers a prolonged state of chronic migraine that is responsive to daily topiramate. The acute (Fig. 1) and chronic (Fig. 2) GTN models are ideal for assessing rescue or preventive, respectively, migraine treatments.

Figure 1: Acute migraine model in rats. A single GTN injection (10mg/kg, i.p., red arrow on x axis) induced mechanical allodynia in both plantar (left) and periorbital (right) regions, as indicated by a reduction in von Frey withdrawal thresholds compared to baseline (BL). Acute mechanical sensitivity could be reversed by sumatriptan (1mg/kg., s.c.) at 30min, 2hr and 4hrs. Sumatriptan was delivered 1hr following GTN induction. n=10/group; Two-Way Repeated Measures ANOVA followed by Dunnett’s, *p<0.05, **p<0.01 vs GTN at the same timepoint, #### p<0.0001, ###p<0.001 vs BL.

Figure 2: Chronic migraine model in rats. Prolonged GTN administration (4 x 10mg/kg over 7 days, i.p., red arrows on x axis) induced mechanical allodynia in both plantar (left) and periorbital (right) regions, as indicated by a reduction in von Frey withdrawal thresholds compared to baseline (BL). Von Frey measurements on test days were conducted prior to GTN injection and thus represent development of chronic sensitivity. Development of mechanical allodynia could be prevented by topiramate (30mg/kg. daily for 9 days, i.p.). n=10/group; Two-Way Repeated Measures ANOVA followed by Dunnett’s, *p<0.05, **p<0.01, ***p<0.001 vs GTN at the same timepoint, ####p<0.0001, ###p<0.001 vs BL.