Injecting wild type mice with glyceryl trinitrate (a.k.a. nitroglycerin, NTG) is a fast and robust method to induce a migraine-like symptomatology that can efficiently be treated with an available migraine medication. Migraine, and its associated headache and neurological symptoms, is a severely impairing condition affecting more than a billion people worldwide. Although migraine is one of the most common neurologic disorders, not much is known about it yet, highlighting the need for a fast turnaround model to study this condition.
Single (day 1) and repeated treatment every other day for 9 days with nitroglycerin (NTG) increases nociception as measured with the grimace scale in wild type mice (Fig.1B). Nociception can be returned to baseline levels by treating mice with sumatriptan. One week after the last NTG injection (day 16), all groups are back to nociceptive baseline level, indicating an acute effect of NTG treatment (Fig.1B).
Figure 1: Effects of acute (day 1) and repeated (day 1-9) injection of nitroglycerin (NTG) on nociceptive response indicating a migraine-like symptomatic in wild type mice. (A) wild type mice, 3 months of age, were injected with nitroglycerin alone (NTG; 10 mg/kg, i.p.) or together with sumatriptan (Suma; 0.6 mg/kg, i.p.), and control according to the injection regime. (B) Score of facial expression associated with migraine-like nociceptive response. High scores indicate migraine-like symptoms. Grimace scale was scored on underlined days 1, 9 and 16, 2 hours after injection. Day 1 and 9: n = 24 / group, day 16: n = 12 / group; two-way ANOVA with Bonferroni post hoc test; Mean ± SEM. **p<0.01, ***p<0.001.
Migraine disproportionally affects female patients over male in a ratio of 3 to 1. However, in this mouse model, both sexes exhibit nitroglycerin-induced headache symptoms (Fig. 2), validating it as a model for migraine studies in both sexes.
Figure 2: Effects of nitroglycerin (NTG) injection in male (A) and female (B) mice on nociceptive response. Separation of data shown in Figure 1 by sex. Day 1 and 9: n = 12 / group, day 16: n = 6 / group; two-way ANOVA with Bonferroni post hoc test; Mean ± SEM. **p<0.01, ***p<0.001.
Although characterization of this nitroglycerin-induced migraine model is still ongoing, first results are promising that this model is a fast and robust option to study migraine pathology in vivo.