Nitroglycerin-induced migraine targetable by different agents

Acute and chronic nitroglycerin administration in laboratory mice led to increased mechanical hypersensitivity and impacted beam balance and meningeal vasodilation. These effects were targetable by sumatriptan, topiramate, and an anti-PACAP antibody.

Nitroglycerin can be used to induce a migraine-like symptomatology in laboratory mice, which can be efficiently treated with available migraine medication [1]. “After induction, we looked at the acute effect of sumatriptan and chronic effect of topiramate before looking at the treatment effect of an anti-PACAP antibody,” said Dr Charlotte Ernstsen Lauritzen (H. Lundbeck A/S, Denmark) [2]. “We also assessed possible vestibular effects using the balanced beam assay and looked at potential meningeal vasodilation in awake and freely moving mice.”

In a first substudy, nitroglycerin induced acute mechanical hypersensitivity on day 1, which both sumatriptan and topiramate could block: there was a significantly lower 50% mechanical sensitivity in the sumatriptan plus nitroglycerin, topiramate plus nitroglycerin, and vehicle control groups, compared with nitroglycerin alone. In a similar substudy, topiramate (administered daily for 9 days) also blocked chronic nitroglycerin-induced mechanical hypersensitivity. Further to these results, an anti-PACAP antibody blocked the mechanical hypersensitivity induced by nitroglycerin, both in an acute (day 1) and chronic (day 9) model (P<0.005 for both). In the balanced beam assay, acute nitroglycerin led to an increased time for animals to cross a balance beam, while chronic nitroglycerin increased the foot count on the beam (P<0.05 for both). Finally, longitudinal assessment of meningeal vasodilation showed enhanced changes from day 1 to day 9 in nitroglycerin-treated mice (P<0.05) but not in vehicle-treated mice (not significant).

“In summary, we confirmed that nitroglycerin induced mechanical hypersensitivity, and most notably, we saw that this could be blocked acutely and chronically with an anti-PACAP antibody,” said Dr Ernstsen Lauritzen. “We saw that nitroglycerin affects dynamic balance, which could be relevant in vestibular migraine studies. We also saw that both acute and chronic nitroglycerin administration induces vasodilation of meningeal arteries, with chronic nitroglycerin leading to enhanced dilation, suggesting migraine-like sensitisation in disease-relevant tissues.”

1. Pradhan AA, et al. Pain. 2014 Feb;155(2):269-274.
2. Ernstsen Lauritzen C, et al. Pharmaceutical insights into nitroglycerin effects on meningeal blood vessel imaging, sensory threshold, and motor function in mice. 18^th European Headache Congress, 4–7 December 2024, Rotterdam, the Netherlands.

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Posted on 6 January 20256 January 2025